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Peripheral inflammation and neurodegeneration; a potential for therapeutic intervention in Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS)



Degeneration of the central nervous system (CNS), also known as neurodegeneration, describes an age-associated progressive loss of the structure and function of neuronal materials, leading to functional and mental impairments.

Main body

Neuroinflammation contributes to the continuous worsening of neurodegenerative states which are characterised by functional and mental impairments due to the progressive loss of the structure and function of neuronal materials. Some of the most common neurodegenerative diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Whilst neuroinflammation is a key contributor to the progression of such disease states, it is not the single cause as there are multiple factors which contribute. Theoretically, non-steroidal anti-inflammatory drugs (NSAIDs) have potential to target neuroinflammation to reduce the severity of disease states. Whilst some animal models investigating the effects of NSAIDs on the risk of neurodegenerative diseases have shown a beneficial effect, this is not always the case and a large number of clinical trials have not shown the same finding.


Further investigation using more advanced research methods is required to better understand neuroinflammatory pathways and understand if there is still a potential window for NSAID efficacy.


Degeneration of the central nervous system (CNS), also known as neurodegeneration, describes an age-associated progressive loss of the structure and function of neuronal materials, leading to functional and mental impairments [1]. Neurodegeneration is a feature of many incurable and, eventually, debilitating neurodegenerative diseases [2]. As the population’s life expectancy continues to rise and the size of the aging population, subsequently, steadily increases [3], the threat of neurodegenerative diseases continues to worsen. For example, between the years 1960 and 2010, the life expectancy at birth in the EU had risen by an astounding 11 years [4]. Some of the most common neurodegenerative disorders include Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS).

Over the years, a growing understanding of the mechanisms underlying the pathophysiology of such disorders has shown continual improvement. The development of experimental model systems which recapitulate characteristic hallmarks of these neurodegenerative disorders has significantly aided such a progression of insight, including the use of yeast, fruit flies, nematode worms and, more commonly, particularly recently, mice [5,6,7,8,9]. More recent advancements have capacitated the ability to produce induced pluripotent stem cells (iPSCs) from differentiated human cells to generate human models of these diseases through the production of patient-specific cell lines in a tissue culture dish [10]. Furthermore, in recent years, these cells have also been cultured in three dimensions, for the first time, producing organoids which represent human tissues including the brain [11, 12]. As these advancements continue to progress, the held understanding of these states follows.

It is now accepted that neuroinflammation, inflammation within the brain or spinal cord, contributes greatly to the overall process of neurodegeneration. Inflammation is the first line of defence of an organism in response to an initial insult, so neuroinflammation is an inherent mechanism which has the purpose of protecting and re-establishing the normal structure and function of the brain, by aiding the recovery of injured neurons, such as in response to infection [13]. Following an infection or inflammatory condition, peripheral immune activation causes the innate immune response to signal to the brain and upregulate cytokine production by the CNS [14]. Whilst the intended purpose of neuroinflammation is beneficial through seeking to overcome the potential threat, if the magnitude or duration of the inflammation is too large or prolonged, respectively, then this process will take a different course. Chronic inflammation has deleterious effects and exacerbates the degree of neurodegenerative states [15].

Although it is believed to be a significant contributor of the most common neurodegenerative diseases, controversy lies in the extent to which peripheral inflammation may be considered a cause of the fatality of neurodegenerative disorders. Gaining a clearer understanding of this will elucidate whether therapeutic intervention involving inhibition of this process may be an effective means of reversing disease progression or, at least, slowing it. The remainder of this review will consider the extent to which peripheral inflammation contributes to neurodegeneration and may be considered a cause of these diseases, in addition to potential therapeutic avenues which have been, or are beginning to be, considered. In order to explore this, AD, PD and ALS will be considered as representations of neurodegenerative states.

Main text

There are several factors which may induce inflammation in the CNS including bacterial infections, viral infections or neuroimmune conditions [16]. Neuroinflammation is an expected feature of the ordinary aging brain although the process is hastened in neurodegenerative states [17]. An acute inflammatory response of the CNS is caused by an immediate activation of glial cells in response to noxious stimuli. When this response is sustained, it leads, ultimately, to neurodegeneration as the blood–brain barrier (BBB) becomes disrupted, allowing an influx of inflammatory cells along with other products with properties that may cause tissue destruction. Elevated levels of inflammatory cytokines in the serum and CNS are also found. In the CNS, proinflammatory cytokines are produced by microglia and astrocytes, the residential immune cells of the CNS which are key to the regulation of brain homeostasis all the way from development, through to adulthood and even aging [18].

Figures 1, 2 and 3 depict this innate immune response.

Fig. 1
figure 1

Adapted from Banjara and Ghost [95]

A schematic depicting the innate response to brain injury. Damage-associated molecular patterns (DAMPs) are sensed by microglia, astrocytes and macrophages causing an increased permeability of the BBB enabling immune cell migration to the sites of tissue damage where inflammatory processes begin to occur through the release of inflammatory mediators.

Fig. 2
figure 2

Adapted from Träger and Tabrizi [96]

A schematic depicting peripheral and central immune dysfunction in neurodegeneration caused by cell-intrinsic expression of mHTT and its effects on cellular processes.

Fig. 3
figure 3

Adapted from Träger and Tabrizi [96]

A schematic depicting routes by which the peripheral immune activation influences neurodegeneration. (1) Mediators of peripheral inflammation and cells are permeable to the brain through circumventricular organs deficient of BBB. (2) Some selected immune mediators, like IL-6, are transported actively across the BBB. (3) Also immune mediators such as IL-1β can result to brain endothelium activation, thereby secreting nitric oxide, cytokines and immunological mediators into the brain. (4) Peripheral immune cells penetrate the brain either directly via the BBB, through the CSF (choroid plexus), thus contributing neurodegeneration. However, it is still unclear the extent to which cells can cross the BBB in neurodegeneration. (5) Finally, peripheral inflammation is translated into the brain through the vagus nerve in the neural reflex which coordinates systemic inflammation by sensing and inhibiting pro-inflammatory markers.

Astrocytes are the most abundant glial cells of the CNS, comprising around 25% of the cerebral volume and are the first cells that CNS-infiltrating immune cells encounter. Microglia comprise around 10% of the entire CNS population, with the function of constantly surveying the microenvironment and producing factors to influence the surrounding astrocytes and neurons. Moreover, in response to pathogen invasion or tissue damage, microglia switch from an inactive (ramified) to an activated (amoeboid) state which promotes an inflammatory response in order to initiate tissue repair [19, 20]. However, the persistence of inflammatory stimuli or failure of normal resolution mechanisms leads to inflammation which occurs in tissue pathology and results in the production of neurotoxic factors which further amplify diseases’ states [21, 22]. Such neurotoxic mediators converge, functionally, to facilitate mechanisms associated with protein degradation, mitochondrial dysfunction, defective axonal transport and apoptosis. These intracellular mechanisms are associated with the pathogenesis of neurodegenerative diseases, such as AD, PD and ALS [1, 15, 23].

The immune response of the CNS is closely controlled in relation to the periphery [15], so an offense causes the release of proinflammatory mediators and this leads to permeabilisation of the BBB. Leukocytes, including T cells and macrophages, which share many functional features with microglia, from the periphery are then able to infiltrate the BBB to reach the CNS [24]. The consequence of this is neuroinflammation. When this response of neuroinflammation is merely acute, such that it is of a reasonable magnitude and limited duration, the effects can be beneficial as potential injury will be minimised through activation of innate immunity. On the other hand, when this is prolonged chronically, a sustained release of inflammatory mediators causes an enhanced degree of oxidative and nitrosative stress which perpetuates the inflammatory cycle and contributes to the progression of neurodegenerative diseases [25, 26].

Neurodegenerative diseases

The most common neurodegenerative diseases are characterised by the pathological accumulation of insoluble filamentous aggregates of normally soluble proteins within the CNS.

A summary of these is given in Table 1.

Table 1 Common neurodegenerative diseases and characteristic proteins

Alzheimer’s disease

Alzheimer’s disease is the most common type of dementia with approximately over 46 million individuals affected worldwide [27] and an expectation that AD will affect around 115.4 million people by 2050 [28]. A progressive decline of cognition, function and behaviour characterises AD with the corresponding symptoms of memory loss, cognitive impairment and unusual behavioural patterns [29]. Underlying this degenerative process is the production of amyloid beta (Aβ) plaques, which are clumps of insoluble peptides formed from the abnormal cleavage of amyloid precursor protein (APP), as well as neurofibrillary tangles (NFTs) formed by the abnormal phosphorylation of Tau protein [30].

In the case of AD, neuroinflammation can be considered part of a characteristic pathological triad involving Aβ plaques and NFTs, with plenty of evidence of an inflammatory response occurring in AD. For example, transgenic mice expressing a Swedish mutation of the APP gene were produced and successfully expressed features of AD pathology, including extensive extracellular Aβ accumulation and neuritic dysfunction. Immunohistochemical analyses then revealed that activated microglia were located in close proximity to the Aβ plaques in addition to a significantly greater production and release of interleukin-1β (IL-1β) and tumour necrosis factor α(TNF- α), two major proinflammatory cytokines, in comparison with such levels associated with inactive microglia [31]. Prior to this study, there was a lack of suitable animal models to support the direct contribution of inflammatory responses to AD pathology. The group was also built on from previous work by avoiding the use of Griffonia simplicifolia GS B4 Isolectin for detection of microglia [32], as it detects both ramified and amoeboid microglia and, instead, using antibodies to CD45 (leukocyte common antigen) and to class I or II major histocompatibility (MHC) antigens, which merely detect activated microglia [33]. Their key findings coincide with those of other studies [34] including in human post-mortem tissue from AD brains [35]. Furthermore, IL-1β pellet implantation in rats has been shown to promote microtubule activation, p38 mitogen-activated protein kinase (MAPK)-mediated hyperphosphorylation of Tau protein as well as a further increase in levels of its own expression [36]. Other studies have shown microglia located in close proximity to Aβ plaques as staining positively for IL-1β in addition to interleukin 6 (IL-6), TNF- α and monocyte chemoattractant protein 1 (MCP-1) [37], which contributes to astrocyte recruitment around plaques [38].

This evidence alludes to a pathway underlying AD aetiology whereby chronic induction of neuronal injury, due to the presence of Aβ plaques and NFTs, generates a self-propagating cycle involving continually rising IL-1β levels. Such injury triggers microglia and astrocytes to become active, through toll-like receptors (TLR) and receptor for advanced glycation end (RAGE)-dependent pathways [39, 40]. Microglia release TNF- α and IL-1β which can also activate astrocytes, and, similarly, astrocyte activation induces further microglial activation [41]. Activation of microglia causes their migration to the plaques to perform phagocytosis; whilst this effect has a protective purpose, when this is prolonged microglia are no longer able to appropriately process Aβ [42, 43]. Instead, microglial activation will be sustained in a feed-forward loop, or microgliosis, resulting in further accumulation of Aβ, production of inflammatory amplifiers and subsequent sustained proinflammatory cytokine signalling, thus exacerbating AD pathology due to the uncontrollable neuronal damage [44, 45]. Effective therapeutic interference of this invasive cycle may serve as a means of slowing down the progression of AD.

Parkinson’s disease

As the second most common neurodegenerative disease, Parkinson’s disease is believed to affect 1–2% of the population aged over 60 years of age [46]. PD results from a preferential loss of dopaminergic neurons of the nigrostriatal pathway, resulting in symptoms of motor impairment including the classical resting tremor, limb rigidity, bradykinesia and postural and gait impairments. The degeneration seen in PD becomes more widespread as the disease progression continues, thus implicating more brain regions [47]. Underlying the pathology of PD are Lewy bodies, which are intra-neuronal cytoplasmic inclusion bodies constituted predominantly of α-synuclein [48, 49].

Similar to AD pathology, peripheral inflammation causing neuroinflammation is involved in the pathology of PD [50]. Highlighting this is the common finding of several studies of an increased proportion of active microglia in the substantia nigra of PD patients, post-mortem [51, 52]. In addition to this, elevated levels of inflammatory amplifiers, such as IL-1β, IL-6 and TNF- α, in both transgenic mice which overexpress α-synuclein and in PD patients, in comparison with wild-type levels and otherwise healthy controls, respectively, were found [53,54,55]. These inflammatory mediators, such as TNF- α, released by activated microglia, disrupt BBB integrity to allow immune cells, macrophages and leukocytes, to enter into the CNS, eventually leading to neuroinflammation [56].

This shows that although neuroinflammation may not be the primary cause of PD, since these findings were observed at symptomatic stages, various models of PD have produced consistent findings, suggesting that neuroinflammation is a crucial contributor to PD progression. Whilst it is clear that microglia and astrocyte activation, via mediators released by injured dopaminergic neurons, is involved, additional in vivo experiments are required for a deeper understanding of the mechanisms underlying this. Such additional insight may aid further development of effective therapeutic strategies which are able to specifically and temporally target inflammatory processes without compromising the potential benefits, such as tissue restoration.

Amyotrophic lateral sclerosis

Another neurodegenerative disease is ALS, which involves progressive deterioration of upper motor neurons (MNs) of the corticospinal tract and lower MNs of the brain stem and ventral roots of the spinal cord, leading to paralysis which, in many cases, is fatal [57, 58]. This process tends to initiate in limbs or bulbar muscles and over time spreads to other regions, eventually resulting in respiratory muscle dysfunction and a consequential respiratory failure. Death usually follows within 2 to 5 years following ALS diagnoses [59]. With no cure, ALS has proven a challenge to treat, as like other neurodegenerative diseases, with only one drug, riluzole, being approved by the Food and Drug Administration as a treatment; however, the mere capacity of this drug is to extend the individual’s life expectancy by approximately 3 months, an effect not nearly profound [60, 61].

Whilst the precise pathogenic mechanisms of ALS remain elusive, pathways which involve oxidative stress, mitochondrial dysfunction, excitotoxicity, neuroinflammation and protein aggregation are believed to comprise a multifactorial nature of ALS [62]. In many cases, ALS roots largely from mutations of superoxide dismutase 1 (SOD1), although other proteins also contribute [63].

There exists a plethora of evidence for the involvement of neuroinflammation in ALS, including the most common observation of increased microglial activation from cerebrospinal fluid analysis and post-mortem spinal cord samples from ALS patients [64,65,66], as well as elevated levels of molecules which amplify inflammation, including Interleukin-8 (IL-8) [67], TNF- α, IL-1β, IL-6 and vascular endothelial growth factor [68]. Furthermore, in a transgenic mouse with SOD1 mutations which exhibited ALS-like characteristics, during the course of symptom progression an increased expression of cyclooxygenase type 2 (COX-2) was detected [17]. COX-2 is an enzyme which plays a role in the synthesis of prostanoids, potent inflammatory mediators, particularly prostaglandin E2 (PGE2) [69]. This was regionally specific; for example, it was seen in the spinal cord but not the cerebellum. Such specificity was not due to an insertional consequence of the transgene, and this is known because the group ensured widespread expression of the mutation. This observation was made in the mice at both early stages of symptom development and also at end stages, in addition to human post-mortem spinal cord samples from ALS patients [70]. The findings of this study highlight a specific role of COX-2 upregulation in neuroinflammation contributing largely to ALS disease progression.

The evidence confirms that neuroinflammation is highly implicated in the motor neuron degeneration seen in ALS, such that signs of neuroinflammation are not only seen in cases where the characteristic symptoms of ALS have already developed, but also during presymptomatic phases of ALS [71]. Therefore, unlike in AD and PD where neuroinflammation seems a consequence of the initial injury underlying the disorders, neuroinflammation acts as both an initiating and propelling factor in the pathogenesis of ALS. However, it is believed that there is a convergence of factors which lead to the onset of ALS, so further research is required to identify the extent to which neuroinflammation, alone, may serve as a trigger for other factors which contribute [72].

Potential for therapeutic intervention

There are currently no cures for neurodegenerative diseases, and treatment options are limited, in terms of options available, efficacy and merely alleviating symptoms rather that underlying causes [73]. Research has enabled a progressively growing understanding on the involvement of peripheral inflammation leading to neuroinflammation, propelling the degeneration underlying AD, PD and ALS, an area with potential for therapeutic intervention. Such therapeutic strategies would be beneficial by targeting these inflammatory processes, perhaps from the earliest stage possible, without restricting the intended protective effects of inflammation, as an innate immune action of the body in response to the initial tissue injury.

Of particular interest as a treatment avenue for AD have been non-steroidal anti-inflammatory drugs (NSAIDs). Experimental models initially suggested that this might be promising. For example, in transgenic mice overexpressing APP, administration of ibuprofen, a non-specific COX inhibitor, at the stage of amyloid plaque formation, caused a decrease in the level of glial activation and plaque density [74, 75]. Another NSAID, indomethacin, was found to attenuate microglial activation and restore impairment of hippocampal long-term potentiation, the primary underlying process of memory loss, thus alleviating the associated memory deficits upon direct Aβ injections into rat dentate gyri [76].

Despite the promising nature of such findings, the success rates of clinical trials do not correspond with this. In several double-blind, randomised, placebo-controlled trials using nonselective NSAIDS, including ibuprofen and indomethacin, as well as those using specific COX-2 inhibitors, no signs of cognitive impairment amelioration were observed [77,78,79,80,81,82]. This was even the case when NSAID treatment was maintained for 4 years [83]. This suggests that NSAID treatment is ineffective once the pathology of AD has already taken its course; however, NSAID administration at early stages of Aβ plaque formation may prevent or reduce the impact of the beneficial aspects of neuroinflammation and this would be counterproductive. On the other hand, when NSAID treatment was provided in patients above the age of 65 years with no clinical impairment at the start of the study, age-associated memory decline was attenuated [84]. This suggests a potential window of NSAID efficacy prior to the onset of disease symptoms, during normal aging processes. In order to successfully execute this treatment method, further investigation trials will be required for NSAID as a preventative measure and non-invasive imaging for the detection of amyloid plaques will be crucial for this.

The success rates of NSAIDs in treating PD do not appear to be any more hopeful. A meta-analysis comparing the results of 17 studies, including many which considered long-term NSAID use, comprised of a total of 2,498,258 participants, found no overall association between NSAIDs and the risk of PD [85]. This finding coincides with that of earlier analyses [86]. NSAIDs are not, therefore, accepted as being associated with PD risk reduction [87]. Due to this, along with the, so far, negative results seen with NSAIDs in AD clinical trials and the potential cardiovascular risks discovered in association with particular NSAIDs, it is unlikely that clinical trials for NSAIDs in PD will be considered. Unfortunately, the evidence suggests the same for ALS [88, 89]. Although some subtle differences on the effects of NSAIDs on the relative risk of developing ALS were found between males and females, these differences are of limited significance and were most likely due to chance or an unacknowledged confounder, particularly as this finding is inconsistent with other studies.

As NSAIDs have proven to be unsuccessful in targeting neuroinflammation to alleviate these neurodegenerative states, this warrants the discovery of novel therapeutic interventions which implicate neuroinflammation. For example, polyphenols, including flavonoids, phenolic acids, phenolic alcohols, stilbenes and lignans, such as those found in apples, berries, citrus fruits, broccoli, cocoa, tea and coffee [90], have been found to target toll-like receptor 4 (TLR4) signalling pathways [91]. TLR4 is found on the cell surface of microglia and is involved in neuroinflammatory pathways as it is a first-line host defence receptor against invasive microorganisms, such that loss of function TLR4 mutations have been shown to inhibit microglial activation [92].

However, other studies have shown that loss of function TLR4 mutations do not influence the immune response in neurodegenerative states in humans [93], suggesting in a physiologic situation that other innate immune response receptors may compensate for TLR4 defects. Despite this, the promising nature of other experimental models and repeated propositions that natural compounds targeting TLR4 may act as vital pharmacophores for the development of effective drugs for the treatment of neurological disorders suggests further investigation should continue. Perhaps, this will require manipulating the TLR4 pathway in a different way or at a more specific and potent stage of disease progression, particularly due to diversity of TLR signalling pathways [94].


Neurodegeneration describes the degeneration of neuronal materials and a subsequent deterioration of CNS function. Inflammation within the CNS, or neuroinflammation, occurs in response to an initial form of tissue injury or damage which varies in different neurodegenerative diseases, such as Aβ plaques and NFTs in AD, α-synuclein forming Lewy bodies in PD and aggregated SOD1 protein in ALS. In neurodegenerative diseases, the purpose of neuroinflammation is to clear up initial infection to ameliorate the severity and progression of the disease; however, when inflammatory stimuli are of too great a magnitude or sustained over a longer period, cytotoxic effects are induced instead due to the persistence of neuroinflammation. The initial injury causes the permeability of the BBB to increase, allowing the migration of activated astrocytes and microglia to the local area and a subsequent release of inflammatory mediators, such as IL-1β, IL-6, IL-8 and TNF- α, thus exacerbating disease states by further facilitating neurodegeneration.

At first glance, targeting neuroinflammatory pathways appears promising as an area for therapeutic intervention, with the expectation that this will slow the disease progression and reduce the severity of symptoms, potentially also lengthening life expectancy. In AD, animal studies exploring the use of NSAIDs produced findings which encouraged further investigation in clinical trials; however, clinical trials were not successful as they showed no link between the use of NSAIDs and risk reduction in AD. In terms of PD and ALS, clinical trials have not been considered due to unsuccessful experimental model trials. Despite this, the notion of partially treating neurodegenerative diseases with NSAIDs is logical and perhaps requires an alternative form of investigation. As mentioned above, three-dimensional models enable realistic analyses of cell-to-cell interactions in physiological situations and in greater depth. As glial cells are highly implicated in neuroinflammatory processes which contribute to neurodegeneration, incorporating neuron–glial interactions into such three-dimensional brain organoid models will aid the elucidation of cell non-autonomous disease mechanisms and may help to yield results which are representative of more accurate human outcomes. This will help a more thorough understanding of precise neuroinflammatory pathways to be obtained and subsequently to clarify whether or not NSAIDs may be still be useful by manipulating neuroinflammatory processes more specifically, such as at precise stages of progression.

Neuroinflammation is a major contributor to neurodegenerative disease progression, although may not be considered a cause in itself as they are typically of a multi-factorial nature. Whilst NSAIDs have not been completely effective in reducing the risk of neurodegenerative disorders in humans, the possibility of this should not be ruled out until advancements in research technologies and processes have been put into action. In the meantime, alternative treatment avenues continue to draw interest for researchers, such as polyphenols which target TLR4 pathways.

Availability of data materials

Data sharing is not applicable to this article as no data sets were generated or analysed during the current study.



Alzheimer’s disease


Parkinson’s disease


Amyotrophic lateral sclerosis


Central nervous system


Induced pluripotent stem cells


Blood–brain barrier


Amyloid beta


Amyloid precursor protein


Neurofibrillary tangles




Tumour necrosis factor a


Cluster of differentiation


Major histocompatibility complex


Mitogen-activated protein kinase


Monocyte chemoattractant protein


Toll-like receptor


Receptor for advanced glycation end


Motor neurons


Cyclooxygenase type 2


Prostaglandin E2


Superoxide dismutase 1


Interleukin 8


Interleukin 6


Non-steroidal anti-inflammatory drugs


Toll-like receptor 4


  1. Ramanan VK, Saykin AJ. Pathways to neurodegeneration: mechanistic insights from GWAS in Alzheimer’s disease, Parkinson’s disease, and related disorders. Am J Neurodegener Dis. 2013;2(3):145–75.

    PubMed  PubMed Central  Google Scholar 

  2. Gitler AD, Dhillon P, Shorter J. Neurodegenerative disease: models, mechanisms, and a new hope. Dis Model Mech. 2017;10(5):499–502.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. Heemels M-T. Neurodegenerative diseases. Nature. 2016;539(7628):179.

    PubMed  Article  Google Scholar 

  4. The 2012 Ageing Report: Economic and budgetary projections for the 27 EU Member States (2010–2060) - European Commission [Internet]. [cited 2020 May 29].

  5. Auluck PK, Chan HYE, Trojanowski JQ, Lee VMY, Bonini NM. Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson’s disease. Science. 2002;295(5556):865–8.

    CAS  PubMed  Article  Google Scholar 

  6. Becker LA, Huang B, Bieri G, Ma R, Knowles DA, Jafar-Nejad P, et al. Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice. Nature. 2017;544(7650):367–71.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. Cooper AA, Gitler AD, Cashikar A, Haynes CM, Hill KJ, Bhullar B, et al. Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson’s models. Science. 2006;313(5785):324–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. Krobitsch S, Lindquist S. Aggregation of huntingtin in yeast varies with the length of the polyglutamine expansion and the expression of chaperone proteins. Proc Natl Acad Sci U S A. 2000;97(4):1589–94.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  9. Link CD. Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1995;92(20):9368–72.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  10. Han SSW, Williams LA, Eggan KC. Constructing and deconstructing stem cell models of neurological disease. Neuron. 2011;70(4):626–44.

    CAS  PubMed  Article  Google Scholar 

  11. Rm M, Sp P. Neural differentiation in the third dimension: generating a human midbrain. Cell Stem Cell. 2016;19(2):145–6.

    Article  CAS  Google Scholar 

  12. Paşca AM, Sloan SA, Clarke LE, Tian Y, Makinson CD, Huber N. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat Methods. 2015;12(7):671–8.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  13. More SV, Kumar H, Kim IS, Song S-Y, Choi D-K. Cellular and molecular mediators of neuroinflammation in the pathogenesis of Parkinson’s disease. Mediators Inflamm. 2013;2013:952375.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  14. Lampa J, Westman M, Kadetoff D, Agréus AN, Le Maître E, Gillis-Haegerstrand C, et al. Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice. Proc Natl Acad Sci U S A. 2012;109(31):12728–33.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. Chen W-W, Zhang X, Huang W-J. Role of neuroinflammation in neurodegenerative diseases (Review). Mol Med Rep. 2016;13(4):3391–6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. Prendergast CT, Anderton SM. Immune cell entry to central nervous system–current understanding and prospective therapeutic targets. Endocr Metab Immune Disord Drug Targets. 2009;9(4):315–27.

    CAS  PubMed  Article  Google Scholar 

  17. Moore AH, Bigbee MJ, Boynton GE, Wakeham CM, Rosenheim HM, Staral CJ, et al. Non-steroidal anti-inflammatory drugs in Alzheimer’s disease and Parkinson’s disease: reconsidering the role of neuroinflammation. Pharmaceuticals. 2010;3(6):1812–41.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. Schwartz M, Kipnis J, Rivest S, Prat A. How do immune cells support and shape the brain in health, disease, and aging? J Neurosci Off J Soc Neurosci. 2013;33(45):17587–96.

    CAS  Article  Google Scholar 

  19. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140(6):918–34.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol (Berl). 2010;119(1):7–35.

    Article  Google Scholar 

  21. Das SJ. Microglia-mediated neuroinflammation is an amplifier of virus-induced neuropathology. J Neurovirol. 2014;20(2):122–36.

    Article  CAS  Google Scholar 

  22. Lull ME, Block ML. Microglial activation and chronic neurodegeneration. Neurother J Am Soc Exp Neurother. 2010;7(4):354–65.

    CAS  Google Scholar 

  23. Taylor JP, Hardy J, Fischbeck KH. Toxic proteins in neurodegenerative disease. Science. 2002;296(5575):1991–5.

    CAS  PubMed  Article  Google Scholar 

  24. Noh H, Jeon J, Seo H. Systemic injection of LPS induces region-specific neuroinflammation and mitochondrial dysfunction in normal mouse brain. Neurochem Int. 2014;69:35–40.

    CAS  PubMed  Article  Google Scholar 

  25. Block ML, Hong J-S. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol. 2005;76(2):77–98.

    CAS  PubMed  Article  Google Scholar 

  26. Rivest S. Regulation of innate immune responses in the brain. Nat Rev Immunol. 2009;9(6):429–39.

    CAS  PubMed  Article  Google Scholar 

  27. Prince MJ. World Alzheimer Report 2015: The Global Impact of Dementia [Internet]. 2015 [cited 2020 May 29].

  28. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement J Alzheimers Assoc. 2013;9(1):63-75.e2.

    Article  Google Scholar 

  29. Neugroschl J, Wang S. Alzheimer’s disease: diagnosis and treatment across the spectrum of disease severity. Mt Sinai J Med N Y. 2011;78(4):596–612.

    Article  Google Scholar 

  30. Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 2011;1(1):a006189.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  31. Benzing WC, Wujek JR, Ward EK, Shaffer D, Ashe KH, Younkin SG, et al. Evidence for glial-mediated inflammation in aged APP(SW) transgenic mice. Neurobiol Aging. 1999;20(6):581–9.

    CAS  PubMed  Article  Google Scholar 

  32. Frautschy SA, Yang F, Irrizarry M, Hyman B, Saido TC, Hsiao K, et al. Microglial response to amyloid plaques in APPsw transgenic mice. Am J Pathol. 1998;152(1):307–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Masliah E, Mallory M, Hansen L, Alford M, Albright T, Terry R, et al. Immunoreactivity of CD45, a protein phosphotyrosine phosphatase Alzheimer’s disease. Acta Neuropathol (Berl). 1991;83(1):12–20.

    CAS  Article  Google Scholar 

  34. Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, et al. In-vivo measurement of activated microglia in dementia. Lancet Lond Engl. 2001;358(9280):461–7.

    CAS  Article  Google Scholar 

  35. Lue LF, Walker DG, Rogers J. Modeling microglial activation in Alzheimer’s disease with human postmortem microglial cultures. Neurobiol Aging. 2001;22(6):945–56.

    CAS  PubMed  Article  Google Scholar 

  36. Sheng W, Yang F, Zhou Y, Yang H, Low PY, Kemeny DM, et al. STAT5 programs a distinct subset of GM-CSF-producing T helper cells that is essential for autoimmune neuroinflammation. Cell Res. 2014;24(12):1387–402.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, et al. Inflammation and Alzheimer’s disease. Neurobiol Aging. 2000;21(3):383–421.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F, et al. Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med. 2003;9(4):453–7.

    CAS  PubMed  Article  Google Scholar 

  39. Drexler SK, Foxwell BM. The role of toll-like receptors in chronic inflammation. Int J Biochem Cell Biol. 2010;42(4):506–18.

    CAS  PubMed  Article  Google Scholar 

  40. Kierdorf K, Fritz G. RAGE regulation and signaling in inflammation and beyond. J Leukoc Biol. 2013;94(1):55–68.

    CAS  PubMed  Article  Google Scholar 

  41. Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, et al. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell. 2009;137(1):47–59.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. Bolmont T, Haiss F, Eicke D, Radde R, Mathis CA, Klunk WE, et al. Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance. J Neurosci Off J Soc Neurosci. 2008;28(16):4283–92.

    CAS  Article  Google Scholar 

  43. Stalder M, Phinney A, Probst A, Sommer B, Staufenbiel M, Jucker M. Association of microglia with amyloid plaques in brains of APP23 transgenic mice. Am J Pathol. 1999;154(6):1673–84.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  44. Hickman SE, Allison EK, El Khoury J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J Neurosci Off J Soc Neurosci. 2008;28(33):8354–60.

    CAS  Article  Google Scholar 

  45. Meda L, Cassatella MA, Szendrei GI, Otvos L, Baron P, Villalba M, et al. Activation of microglial cells by beta-amyloid protein and interferon-gamma. Nature. 1995;374(6523):647–50.

    CAS  PubMed  Article  Google Scholar 

  46. Massano J, Bhatia KP. Clinical approach to Parkinson’s disease: features, diagnosis, and principles of management. Cold Spring Harb Perspect Med. 2012;2(6):a008870.

    PubMed  PubMed Central  Article  Google Scholar 

  47. Braak H, Del Tredici K, Rüb U, de Vos RAI, Jansen Steur ENH, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24(2):197–211.

    PubMed  Article  Google Scholar 

  48. Dickson DW. Parkinson’s disease and parkinsonism: neuropathology. Cold Spring Harb Perspect Med. 2012;2(8).

  49. Moore DJ, West AB, Dawson VL, Dawson TM. Molecular pathophysiology of Parkinson’s disease. Annu Rev Neurosci. 2005;28:57–87.

    CAS  PubMed  Article  Google Scholar 

  50. McGeer PL, McGeer EG. Glial reactions in Parkinson’s disease. Mov Disord Off J Mov Disord Soc. 2008;23(4):474–83.

    Article  Google Scholar 

  51. Damier P, Hirsch EC, Zhang P, Agid Y, Javoy-Agid F. Glutathione peroxidase, glial cells and Parkinson’s disease. Neuroscience. 1993;52(1):1–6.

    CAS  PubMed  Article  Google Scholar 

  52. McGeer EG, McGeer PL. The importance of inflammatory mechanisms in alzheimer disease. Exp Gerontol. 1998;33(5):371–8.

    CAS  PubMed  Article  Google Scholar 

  53. Blum-Degen D, Müller T, Kuhn W, Gerlach M, Przuntek H, Riederer P. Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinson’s disease patients. Neurosci Lett. 1995;202(1–2):17–20.

    CAS  PubMed  Article  Google Scholar 

  54. Mogi M, Harada M, Kondo T, Riederer P, Inagaki H, Minami M, et al. Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci Lett. 1994;180(2):147–50.

    CAS  PubMed  Article  Google Scholar 

  55. Su B, Wang X, Nunomura A, Moreira PI, Lee H-G, Perry G, et al. Oxidative stress signaling in Alzheimer’s disease. Curr Alzheimer Res. 2008;5(6):525–32.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. Rezai-Zadeh K, Gate D, Town T. CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease? J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol. 2009;4(4):462–75.

    Article  Google Scholar 

  57. Rowland LP. Amyotrophic lateral sclerosis. Curr Opin Neurol. 1994;7(4):310–5.

    CAS  PubMed  Article  Google Scholar 

  58. Liu J, Wang F. Role of neuroinflammation in amyotrophic lateral sclerosis: cellular mechanisms and therapeutic implications. Front Immunol. 2017;8:1005.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  59. Rothstein JD. Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Ann Neurol. 2009;65(S1):S3-9.

    CAS  PubMed  Article  Google Scholar 

  60. Kumar V, Islam A, Hassan MI, Ahmad F. Therapeutic progress in amyotrophic lateral sclerosis-beginning to learning. Eur J Med Chem. 2016;4(121):903–17.

    Article  CAS  Google Scholar 

  61. Miller RG, Mitchell JD, Lyon M, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2002;(2):CD001447.

  62. Geevasinga N, Menon P, Özdinler PH, Kiernan MC, Vucic S. Pathophysiological and diagnostic implications of cortical dysfunction in ALS. Nat Rev Neurol. 2016;12(11):651–61.

    CAS  PubMed  Article  Google Scholar 

  63. Wiedau-Pazos M, Goto JJ, Rabizadeh S, Gralla EB, Roe JA, Lee MK, et al. Altered reactivity of superoxide dismutase in familial amyotrophic lateral sclerosis. Science. 1996;271(5248):515–8.

    CAS  PubMed  Article  Google Scholar 

  64. Graves MC, Fiala M, Dinglasan LAV, Liu NQ, Sayre J, Chiappelli F, et al. Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells. Amyotroph Lateral Scler Mot Neuron Disord Off Publ World Fed Neurol Res Group Mot Neuron Dis. 2004;5(4):213–9.

    CAS  Google Scholar 

  65. Philips T, Robberecht W. Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol. 2011;10(3):253–63.

    CAS  PubMed  Article  Google Scholar 

  66. D. SS, J. B, C. LA, H T. Biochemical markers in CSF of ALS patients. Curr Med Chem. 2008;15(18):1788–1801.

  67. Kuhle J, Lindberg RLP, Regeniter A, Mehling M, Steck AJ, Kappos L, et al. Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis. Eur J Neurol. 2009;16(6):771–4.

    CAS  PubMed  Article  Google Scholar 

  68. Hu Y, Cao C, Qin X-Y, Yu Y, Yuan J, Zhao Y, et al. Increased peripheral blood inflammatory cytokine levels in amyotrophic lateral sclerosis. Sci Rep. 2017;7(1):9094.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  69. Seibert K, Masferrer JL. Role of inducible cyclooxygenase (COX-2) in inflammation. Receptor. 1994;4(1):17–23.

    CAS  PubMed  Google Scholar 

  70. Almer G, Guégan C, Teismann P, Naini A, Rosoklija G, Hays AP, et al. Increased expression of the pro-inflammatory enzyme cyclooxygenase-2 in amyotrophic lateral sclerosis. Ann Neurol. 2001;49(2):176–85.

    CAS  PubMed  Article  Google Scholar 

  71. Komine O, Yamanaka K. Neuroinflammation in motor neuron disease. Nagoya J Med Sci. 2015;77(4):537–49.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Martin S, Al Khleifat A, Al-Chalabi A. What causes amyotrophic lateral sclerosis? F1000Research. 2017;6:371.

  73. Chen X, Pan W. The treatment strategies for neurodegenerative diseases by integrative medicine. Integr Med Int. 2014;1(4):223–5.

    Article  Google Scholar 

  74. Yan Q, Zhang J, Liu H, Babu-Khan S, Vassar R, Biere AL, et al. Anti-inflammatory drug therapy alters beta-amyloid processing and deposition in an animal model of Alzheimer’s disease. J Neurosci Off J Soc Neurosci. 2003;23(20):7504–9.

    CAS  Article  Google Scholar 

  75. Lim GP, Yang F, Chu T, Chen P, Beech W, Teter B, et al. Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer’s disease. J Neurosci Off J Soc Neurosci. 2000;20(15):5709–14.

    CAS  Article  Google Scholar 

  76. Dong Z, Han H, Li H, Bai Y, Wang W, Tu M, et al. Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis. J Clin Invest. 2015;125(1):234–47.

    PubMed  Article  Google Scholar 

  77. Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA. 2003;289(21):2819–26.

    CAS  PubMed  Article  Google Scholar 

  78. Aisen PS, Schmeidler J, Pasinetti GM. Randomized pilot study of nimesulide treatment in Alzheimer’s disease. Neurology. 2002;58(7):1050–4.

    CAS  PubMed  Article  Google Scholar 

  79. de Jong D, Jansen R, Hoefnagels W, Jellesma-Eggenkamp M, Verbeek M, Borm G, et al. No Effect of One-Year Treatment with Indomethacin on Alzheimer’s Disease Progression: A Randomized Controlled Trial. PLoS ONE [Internet]. 2008 Jan 23 [cited 2020 May 29];3(1).

  80. Pasqualetti P, Bonomini C, Dal Forno G, Paulon L, Sinforiani E, Marra C, et al. A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer’s disease. Aging Clin Exp Res. 2009;21(2):102–10.

    CAS  PubMed  Article  Google Scholar 

  81. Reines SA, Block GA, Morris JC, Liu G, Nessly ML, Lines CR, et al. Rofecoxib: no effect on Alzheimer’s disease in a 1-year, randomized, blinded, controlled study. Neurology. 2004;62(1):66–71.

    CAS  PubMed  Article  Google Scholar 

  82. Soininen H, West C, Robbins J, Niculescu L. Long-term efficacy and safety of celecoxib in Alzheimer’s disease. Dement Geriatr Cogn Disord. 2007;23(1):8–21.

    CAS  PubMed  Article  Google Scholar 

  83. Thal LJ, Ferris SH, Kirby L, Block GA, Lines CR, Yuen E, et al. A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2005;30(6):1204–15.

    CAS  Article  Google Scholar 

  84. Small GW, Siddarth P, Silverman DHS, Ercoli LM, Miller KJ, Lavretsky H, et al. Cognitive and cerebral metabolic effects of celecoxib versus placebo in people with age-related memory loss: randomized controlled study. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry. 2008;16(12):999–1009.

    Article  Google Scholar 

  85. Poly TN, Islam MMR, Yang H-C, Li Y-CJ. Non-steroidal anti-inflammatory drugs and risk of Parkinson’s disease in the elderly population: a meta-analysis. Eur J Clin Pharmacol. 2019;75(1):99–108.

  86. Samii A, Etminan M, Wiens MO, Jafari S. NSAID use and the risk of Parkinson’s disease: systematic review and meta-analysis of observational studies. Drugs Aging. 2009;26(9):769–79.

    CAS  PubMed  Article  Google Scholar 

  87. Ren L, Yi J, Yang J, Li P, Cheng X, Mao P. Nonsteroidal anti-inflammatory drugs use and risk of Parkinson disease. Medicine (Baltimore) [Internet]. 2018 Sep 14 [cited 2020 May 29];97(37).

  88. Fondell E, O’Reilly ÉJ, Fitzgerald KC, Falcone GJ, McCullough ML, Thun MJ, et al. Non-steroidal anti-inflammatory drugs and amyotrophic lateral sclerosis: results from five prospective cohort studies. Amyotroph Lateral Scler Off Publ World Fed Neurol Res Group Mot Neuron Dis. 2012;13(6):573–9.

    CAS  Google Scholar 

  89. Popat RA, Tanner CM, van den Eeden SK, Bernstein AL, Bloch DA, Leimpeter A, et al. Effect of non-steroidal anti-inflammatory medications on the risk of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Off Publ World Fed Neurol Res Group Mot Neuron Dis. 2007;8(3):157–63.

    CAS  Google Scholar 

  90. Williamson G. The role of polyphenols in modern nutrition. Nutr Bull. 2017;42(3):226–35.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  91. Rahimifard M, Maqbool F, Moeini-Nodeh S, Niaz K, Abdollahi M, Braidy N, et al. Targeting the TLR4 signaling pathway by polyphenols: a novel therapeutic strategy for neuroinflammation. Ageing Res Rev. 2017;36:11–9.

    CAS  PubMed  Article  Google Scholar 

  92. Walter S, Letiembre M, Liu Y, Heine H, Penke B, Hao W, et al. Role of the toll-like receptor 4 in neuroinflammation in Alzheimer’s disease. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol. 2007;20(6):947–56.

    CAS  Article  Google Scholar 

  93. Feterowski C, Emmanuilidis K, Miethke T, Gerauer K, Rump M, Ulm K, et al. Effects of functional Toll-like receptor-4 mutations on the immune response to human and experimental sepsis. Immunology. 2003;109(3):426–31.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  94. Akira S, Takeda K. Functions of toll-like receptors: lessons from KO mice. C R Biol. 2004;327(6):581–9.

    CAS  PubMed  Article  Google Scholar 

  95. Banjara M, Ghosh C. Sterile neuroinflammation and strategies for therapeutic intervention. Int J Inflam. 2017;2017:8385961.

  96. Träger U, Tabrizi SJ. Peripheral inflammation in neurodegeneration. J Mol Med Berl Ger. 2013;91(6):673–81.

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LH contributed to conception and design of the work. EP was involved in drafting the work, as well as designed the work. CI designed, drafted and revised the work. EM designed as well as revised the work. GI was involved in drafting of the work as well as revision. All authors have read and approved the final manuscript.

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Hanna, L., Poluyi, E., Ikwuegbuenyi, C. et al. Peripheral inflammation and neurodegeneration; a potential for therapeutic intervention in Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Egypt J Neurosurg 37, 15 (2022).

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  • Neuroinflammation
  • Neurodegeneration
  • Intervention