Sochocka M, et al. The gut microbiome alterations and inflammation-driven pathogenesis of Alzheimer's disease-a critical review. Mol Neurobiol. 2019;56:1841–51.
CAS
PubMed
Google Scholar
Niedzielska E, et al. Oxidative stress in neurodegenerative diseases. Mol Neurobiol. 2016;53:4094–125.
CAS
PubMed
Google Scholar
Fraser PA. The role of free radical generation in increasing cerebrovascular permeability. Free Radic Biol Med. 2011;51:967–77.
CAS
PubMed
Google Scholar
Abdul-Muneer PM, Chandra N, Haorah J. Interactions of oxidative stress and neurovascular inflammation in the pathogenesis of traumatic brain injury. Mol Neurobiol. 2015;51:966–79.
CAS
PubMed
Google Scholar
Abdul-Muneer PM, et al. Induction of oxidative and nitrosative damage leads to cerebrovascular inflammation in an animal model of mild traumatic brain injury induced by primary blast. Free Radic Biol Med. 2013;60:282–91.
CAS
PubMed
PubMed Central
Google Scholar
Hwang I, et al. Peroxiredoxin 3 deficiency accelerates chronic kidney injury in mice through interactions between macrophages and tubular epithelial cells. Free Radic Biol Med. 2019;131:162–72.
CAS
PubMed
Google Scholar
Kono H, Rock KL. How dying cells alert the immune system to danger. Nat Rev Immunol. 2008;8:279–89.
CAS
PubMed
PubMed Central
Google Scholar
Chen GY, Nuñez G. Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol. 2010;10:826–37.
CAS
PubMed
PubMed Central
Google Scholar
Shi Y, Evans JE, Rock KL. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature. 2003;425:516–21.
CAS
PubMed
Google Scholar
Idzko M, et al. Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells. Nat Med. 2007;13:913–9.
CAS
PubMed
Google Scholar
Inoue K. Microglial activation by purines and pyrimidines. Glia. 2002;40:156–63.
PubMed
Google Scholar
Hu Y, et al. mTOR-mediated metabolic reprogramming shapes distinct microglia functions in response to lipopolysaccharide and ATP. Glia. 2019.
Cserép C, et al. Microglia monitor and protect neuronal function via specialized somatic purinergic junctions: Science; 2019.
Cao X, et al. Astrocyte-derived ATP modulates depressive-like behaviors. Nat Med. 2013;19:773–7.
CAS
PubMed
Google Scholar
Yang F, Zhao K, Zhang X, Zhang J, Xu B. ATP Induces disruption of tight junction proteins via IL-1 beta-dependent MMP-9 activation of human blood-brain barrier. Neural Plast. 2016;2016:8928530.
PubMed
PubMed Central
Google Scholar
Subauste CS. The CD40-ATP-P2X. Front Immunol. 2019;10:2958.
CAS
PubMed
PubMed Central
Google Scholar
Suzuki T, et al. Extracellular ADP augments microglial inflammasome and NF-κB activation via the P2Y12 receptor. Eur J Immunol. 2019.
Viviani B, et al. Interleukin-1beta enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci. 2003;23:8692–700.
CAS
PubMed
PubMed Central
Google Scholar
Ising C, et al. NLRP3 inflammasome activation drives tau pathology. Nature. 2019;575:669–73.
CAS
PubMed
PubMed Central
Google Scholar
Gordon R, et al. Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice. Sci Transl Med. 2018;10.
Deora V, et al. The microglial NLRP3 inflammasome is activated by amyotrophic lateral sclerosis proteins. Glia. 2020;68:407–21.
PubMed
Google Scholar
Deroide N, et al. MFGE8 inhibits inflammasome-induced IL-1β production and limits postischemic cerebral injury. J Clin Invest. 2013;123:1176–81.
CAS
PubMed
PubMed Central
Google Scholar
Freeman L, et al. NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia and astrocytes. J Exp Med. 2017;214:1351–70.
CAS
PubMed
PubMed Central
Google Scholar
Kaushal V, et al. Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation. Cell Death Differ. 2015;22:1676–86.
CAS
PubMed
PubMed Central
Google Scholar
Voet S, Srinivasan S, Lamkanfi M, van Loo G. Inflammasomes in neuroinflammatory and neurodegenerative diseases. EMBO Mol Med. 2019;11.
Ginhoux F, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science. 2010;330:841–5.
CAS
PubMed
PubMed Central
Google Scholar
McDonald CL, et al. Inhibiting TLR2 activation attenuates amyloid accumulation and glial activation in a mouse model of Alzheimer's disease. Brain Behav Immun. 2016;58:191–200.
CAS
PubMed
Google Scholar
Kouli A, Horne CB, Williams-Gray CH. Toll-like receptors and their therapeutic potential in Parkinson's disease and α-synucleinopathies. Brain Behav Immun. 2019;81:41–51.
CAS
PubMed
Google Scholar
Wu D, Zhang X, Zhao M, Zhou AL. The role of the TLR4/NF-κB signaling pathway in Aβ accumulation in primary hippocampal neurons. Sheng Li Xue Bao. 2015;67:319–28.
CAS
PubMed
Google Scholar
Gülke E, Gelderblom M, Magnus T. Danger signals in stroke and their role on microglia activation after ischemia. Ther Adv Neurol Disord. 2018;11:1756286418774254.
PubMed
PubMed Central
Google Scholar
B. Relja, W. G. Land, Damage-associated molecular patterns in trauma. Eur J Trauma Emerg Surg, (2019).
Google Scholar
Baruch K, et al. PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease. Nat Med. 2016;22:135–7.
CAS
PubMed
Google Scholar
McGeer PL, McGeer EG. The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathol. 2013;126:479–97.
CAS
PubMed
Google Scholar
Heppner FL, Ransohoff RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci. 2015;16:358–72.
CAS
PubMed
Google Scholar
Prokop S, Miller KR, Heppner FL. Microglia actions in Alzheimer’s disease. Acta Neuropathol. 2013;126:461–77.
CAS
PubMed
Google Scholar
Cai Z, Hussain MD, Yan LJ. Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer's disease. Int J Neurosci. 2014;124:307–21.
CAS
PubMed
Google Scholar
Lee JJ, Wang PW, Yang IH, Wu CL, Chuang JH. Amyloid-beta mediates the receptor of advanced glycation end product-induced pro-inflammatory response via toll-like receptor 4 signaling pathway in retinal ganglion cell line RGC-5. Int J Biochem Cell Biol. 2015;64:1–10.
CAS
PubMed
Google Scholar
Yu Y, Ye RD. Microglial Aβ receptors in Alzheimer's disease. Cell Mol Neurobiol. 2015;35:71–83.
CAS
PubMed
Google Scholar
Shibata M, et al. Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest. 2000;106:1489–99.
CAS
PubMed
PubMed Central
Google Scholar
S. Y. Kook et al., Aβ1-42-RAGE interaction disrupts tight junctions of the blood-brain barrier via Ca2+-calcineurin signaling. J Neurosci 32, 8845-8854 (2012).
Criscuolo C, et al. Entorhinal Cortex dysfunction can be rescued by inhibition of microglial RAGE in an Alzheimer's disease mouse model. Sci Rep. 2017;7:42370.
CAS
PubMed
PubMed Central
Google Scholar
Origlia N, et al. Microglial receptor for advanced glycation end product-dependent signal pathway drives beta-amyloid-induced synaptic depression and long-term depression impairment in entorhinal cortex. J Neurosci. 2010;30:11414–25.
CAS
PubMed
PubMed Central
Google Scholar
Wan W, Chen H, Li Y. The potential mechanisms of Aβ-receptor for advanced glycation end-products interaction disrupting tight junctions of the blood-brain barrier in Alzheimer's disease. Int J Neurosci. 2014;124:75–81.
CAS
PubMed
Google Scholar
Coraci IS, et al. CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer's disease brains and can mediate production of reactive oxygen species in response to beta-amyloid fibrils. Am J Pathol. 2002;160:101–12.
CAS
PubMed
PubMed Central
Google Scholar
Moore KJ, et al. A CD36-initiated signaling cascade mediates inflammatory effects of beta-amyloid. J Biol Chem. 2002;277:47373–9.
CAS
PubMed
Google Scholar
El Khoury JB, et al. CD36 mediates the innate host response to beta-amyloid. J Exp Med. 2003;197:1657–66.
PubMed
PubMed Central
Google Scholar
Chong M, et al. CD36 initiates the secretory phenotype during the establishment of cellular senescence. EMBO Rep. 2018;19.
Guerreiro R, et al. TREM2 variants in Alzheimer's disease. N Engl J Med. 2013;368:117–27.
CAS
PubMed
Google Scholar
Jonsson T, Stefansson K. TREM2 and neurodegenerative disease. N Engl J Med. 2013;369:1568–9.
CAS
PubMed
Google Scholar
Takahashi K, Rochford CD, Neumann H. Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J Exp Med. 2005;201:647–57.
CAS
PubMed
PubMed Central
Google Scholar
Hsieh CL, et al. A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. J Neurochem. 2009;109:1144–56.
CAS
PubMed
PubMed Central
Google Scholar
Song WM, et al. Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism. J Exp Med. 2018;215:745–60.
CAS
PubMed
PubMed Central
Google Scholar
Wang Y, et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model. Cell. 2015;160:1061–71.
CAS
PubMed
PubMed Central
Google Scholar
Y. Zhao et al., TREM2 Is a receptor for β-amyloid that mediates microglial function. Neuron 97, 1023-1031.e1027 (2018).
Jay TR, et al. Disease progression-dependent effects of TREM2 deficiency in a mouse model of Alzheimer's disease. J Neurosci. 2017;37:637–47.
CAS
PubMed
PubMed Central
Google Scholar
H. Keren-Shaul et al., A unique microglia type associated with restricting development of Alzheimer's disease. Cell 169, 1276-1290.e1217 (2017).
A. Griciuc et al., TREM2 acts downstream of CD33 in modulating microglial pathology in Alzheimer's disease. Neuron 103, 820-835.e827 (2019).
M. G. Spillantini, R. A. Crowther, R. Jakes, M. Hasegawa, M. Goedert, alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proc Natl Acad Sci U S A 95, 6469-6473 (1998).
Lashuel HA, Overk CR, Oueslati A, Masliah E. The many faces of α-synuclein: from structure and toxicity to therapeutic target. Nat Rev Neurosci. 2013;14:38–48.
CAS
PubMed
PubMed Central
Google Scholar
Conway KA, Harper JD, Lansbury PT. Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nat Med. 1998;4:1318–20.
CAS
PubMed
Google Scholar
Webb JL, Ravikumar B, Atkins J, Skepper JN, Rubinsztein DC. Alpha-synuclein is degraded by both autophagy and the proteasome. J Biol Chem. 2003;278:25009–13.
CAS
PubMed
Google Scholar
S. J. Wood et al., alpha-synuclein fibrillogenesis is nucleation-dependent. Implications for the pathogenesis of Parkinson's disease. J Biol Chem 274, 19509-19512 (1999).
Brundin P, Li JY, Holton JL, Lindvall O, Revesz T. Research in motion: the enigma of Parkinson's disease pathology spread. Nat Rev Neurosci. 2008;9:741–5.
CAS
PubMed
Google Scholar
Lee EJ, et al. Alpha-synuclein activates microglia by inducing the expressions of matrix metalloproteinases and the subsequent activation of protease-activated receptor-1. J Immunol. 2010;185:615–23.
CAS
PubMed
Google Scholar
Lema Tomé CM, et al. Inflammation and α-synuclein's prion-like behavior in Parkinson's disease--is there a link? Mol Neurobiol. 2013;47:561–74.
PubMed
Google Scholar
Kim C, et al. Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat Commun. 2013;4:1562.
PubMed
Google Scholar
Doorn KJ, et al. Microglial phenotypes and toll-like receptor 2 in the substantia nigra and hippocampus of incidental Lewy body disease cases and Parkinson's disease patients. Acta Neuropathol Commun. 2014;2:90.
PubMed
PubMed Central
Google Scholar
S. G. Daniele et al., Activation of MyD88-dependent TLR1/2 signaling by misfolded α-synuclein, a protein linked to neurodegenerative disorders. Sci Signal 8, ra45 (2015).
Zhang W, et al. Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. FASEB J. 2005;19:533–42.
CAS
PubMed
Google Scholar
Fan Z, et al. Systemic activation of NLRP3 inflammasome and plasma α-synuclein levels are correlated with motor severity and progression in Parkinson's disease. J Neuroinflammation. 2020;17:11.
CAS
PubMed
PubMed Central
Google Scholar
Benner EJ, et al. Nitrated alpha-synuclein immunity accelerates degeneration of nigral dopaminergic neurons. PLoS One. 2008;3:e1376.
PubMed
PubMed Central
Google Scholar
Reynolds AD, et al. Nitrated alpha-synuclein-activated microglial profiling for Parkinson's disease. J Neurochem. 2008;104:1504–25.
CAS
PubMed
Google Scholar
Fellner L, et al. Toll-like receptor 4 is required for α-synuclein dependent activation of microglia and astroglia. Glia. 2013;61:349–60.
PubMed
PubMed Central
Google Scholar
Li Y, et al. CXCL12 is involved in α-synuclein-triggered neuroinflammation of Parkinson's disease. J Neuroinflammation. 2019;16:263.
CAS
PubMed
PubMed Central
Google Scholar
Kitada T, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392:605–8.
CAS
PubMed
Google Scholar
Valente EM, et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 2004;304:1158–60.
CAS
PubMed
Google Scholar
Koyano F, et al. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature. 2014;510:162–6.
CAS
PubMed
Google Scholar
Sliter DA, et al. Parkin and PINK1 mitigate STING-induced inflammation. Nature. 2018;561:258–62.
CAS
PubMed
PubMed Central
Google Scholar
West AP, et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature. 2015;520:553–7.
PubMed
PubMed Central
Google Scholar
Gui C, et al. p38 MAPK-DRP1 signaling is involved in mitochondrial dysfunction and cell death in mutant A53T α-synuclein model of Parkinson's disease. Toxicol Appl Pharmacol. 2019;388:114874.
PubMed
Google Scholar
Faustini G, et al. Alpha-synuclein preserves mitochondrial fusion and function in neuronal cells. Oxid Med Cell Longev. 2019;2019:4246350.
PubMed
PubMed Central
Google Scholar
Mitchell JD, Borasio GD. Amyotrophic lateral sclerosis. Lancet. 2007;369:2031–41.
CAS
PubMed
Google Scholar
Kim HJ, Taylor JP. Lost in transportation: nucleocytoplasmic transport defects in ALS and other neurodegenerative diseases. Neuron. 2017;96:285–97.
CAS
PubMed
PubMed Central
Google Scholar
Arai T, et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun. 2006;351:602–11.
CAS
PubMed
Google Scholar
Neumann M, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314:130–3.
CAS
PubMed
Google Scholar
Weskamp K, et al. Shortened TDP43 isoforms upregulated by neuronal hyperactivity drive TDP43 pathology in ALS. J Clin Invest. 2019.
Zhao W, et al. TDP-43 activates microglia through NF-κB and NLRP3 inflammasome. Exp Neurol. 2015;273:24–35.
CAS
PubMed
Google Scholar
Beers DR, Henkel JS, Zhao W, Wang J, Appel SH. CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc Natl Acad Sci U S A. 2008;105:15558–63.
CAS
PubMed
PubMed Central
Google Scholar
Boillée S, et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science. 2006;312:1389–92.
PubMed
Google Scholar
Yamanaka K, et al. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci. 2008;11:251–3.
CAS
PubMed
PubMed Central
Google Scholar
Meissner F, Molawi K, Zychlinsky A. Mutant superoxide dismutase 1-induced IL-1beta accelerates ALS pathogenesis. Proc Natl Acad Sci U S A. 2010;107:13046–50.
CAS
PubMed
PubMed Central
Google Scholar
Ayers JI, Fromholt SE, O'Neal VM, Diamond JH, Borchelt DR. Prion-like propagation of mutant SOD1 misfolding and motor neuron disease spread along neuroanatomical pathways. Acta Neuropathol. 2016;131:103–14.
CAS
PubMed
Google Scholar
Oono M, et al. Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through interaction with misfolded superoxide dismutase 1. J Neurochem. 2014;128:403–18.
CAS
PubMed
Google Scholar
Maier M, et al. A human-derived antibody targets misfolded SOD1 and ameliorates motor symptoms in mouse models of amyotrophic lateral sclerosis. Sci Transl Med. 2018;10.
Kawamata T, Akiyama H, Yamada T, McGeer PL. Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am J Pathol. 1992;140:691–707.
CAS
PubMed
PubMed Central
Google Scholar
Rentzos M, et al. Interleukin-17 and interleukin-23 are elevated in serum and cerebrospinal fluid of patients with ALS: a reflection of Th17 cells activation? Acta Neurol Scand. 2010;122:425–9.
CAS
PubMed
Google Scholar
Saresella M, et al. T helper-17 activation dominates the immunologic milieu of both amyotrophic lateral sclerosis and progressive multiple sclerosis. Clin Immunol. 2013;148:79–88.
CAS
PubMed
Google Scholar
Chiu IM, et al. T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS. Proc Natl Acad Sci U S A. 2008;105:17913–8.
CAS
PubMed
PubMed Central
Google Scholar
Beers DR, et al. Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain. 2011;134:1293–314.
PubMed
PubMed Central
Google Scholar