nach oben

Neurological Sciences

Erschienen in:

26.05.2020 | Original Article

The role of microglia in the development of neurodegeneration

verfasst von: Aigul R. Saitgareeva, Kirill V. Bulygin, Ilgiz F. Gareev, Ozal A. Beylerli, Leila R. Akhmadeeva

Erschienen in: Neurological Sciences | Ausgabe 12/2020

Einloggen, um Zugang zu erhalten

Abstract

Microglia-mediated central nervous system (CNS) inflammation is one of the key features of various neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases. In the last few years, a number of studies have investigated the link between neurodegenerative diseases and CNS glial cells, in particular microglia. Microglial cells are the main resident immune cells and comprise approximately 10–15% of all CNS cells. Microglia at rest regulates CNS homeostasis via phagocytic activity, by removing pathogens and cell detritus. “Resting” microglia cells transform into an activated form and produce inflammatory mediators, thus protecting neurons and providing defense against invading pathogens. Excessive inflammation leads to neuronal damage and neurodegenerative diseases. Various microglial reactions at different stages of the disease can open up new directions for treatment interventions and modification of the inflammatory activity. This review focuses on the potential role of microglia and the dynamic M1/M2 phenotype changes that are critically linked to certain neurodegenerative diseases.

Kettenmann H, Hanisch U, Noda M, Verkhratsky A (2011) Physiology of microglia. Physiol Rev 91(2):461–553. https://doi.org/10.1152/physrev.00011.2010CrossRefPubMed

Sorrenti V, Contarini G, Sut S, Dall’Acqua S, Confortin F, Pagetta A, Giusti P, Zusso M (2018) Curcumin prevents acute neuroinflammation and long-term memory impairment induced by systemic lipopolysaccharide in mice. Front Pharmacol 9:183. https://doi.org/10.3389/fphar.2018.00183CrossRefPubMedPubMedCentral

Glass C, Saijo K, Winner B, Marchetto M, Gage F (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140(6):918–934. https://doi.org/10.1016/j.cell.2010.02.016CrossRefPubMedPubMedCentral

Xu L, He D, Bai Y (2016) Microglia-mediated inflammation and neurodegenerative disease. Mol Neurobiol 53(10):6709–6715. https://doi.org/10.1007/s12035-015-9593-4CrossRefPubMed

Anderson SA, Vetter ML (2019) Developmental roles of microglia: a window into mechanisms of disease. Dev Dyn 248(1):98–117. https://doi.org/10.1002/dvdy.1CrossRefPubMed

Orihuela R, McPherson CA, Harry GJ (2016) Microglial M1/M2 polarization and metabolic states. B J Pharmacol 173(4):649–666. https://doi.org/10.1111/bph.13139CrossRef

Colton C, Wilcock D (2010) Assessing activation states in microglia. CNS Neurol Disord Drug Targets 9(2):174–191. https://doi.org/10.2174/187152710791012053CrossRefPubMed

Vay SU, Flitsch LG, Rabenstein M, Rogall R, Blaschke S, Kleinhaus J, Reinert N, Bach A, Fink GR, Schroeter M, Rueger MA (2018) The plasticity of primary microglia and their multifaceted effects on endogenous neural stem cells in vitro and in vivo. J Neuroinflammation 15:226. https://doi.org/10.1186/s12974-018-1261-yCrossRefPubMedPubMedCentral

Cherry JD, Olschowka JA, O’Banion MK (2014) Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J Neuroinflammation 11:98. https://doi.org/10.1186/1742-2094-11-98CrossRefPubMedPubMedCentral

10.

Sanjabi S, Oh SA, Li MO (2017) Regulation of the immune response by TGF-β: from conception to autoimmunity and infection. Cold Spring Harb Perspect Biol 9(6):a022236. https://doi.org/10.1101/cshperspect.a022236CrossRefPubMedPubMedCentral

11.

Majerova P, Zilkova M, Kazmerova Z, Kovac A, Paholikova K, Kovacech B, Zilka N, Novak M (2014) Microglia display modest phagocytic capacity for extracellular tau oligomers. J Neuroinflammation 11(1):161. https://doi.org/10.1186/s12974-014-0161-zCrossRefPubMedPubMedCentral

12.

Scarpina F, Paschino C, Priano L, Mauro A (2020) Performance at the clock drawing test of individuals affected by Parkinson’s disease and healthy subjects: a retrospective study. Neurol Sci 41(4):843–849. https://doi.org/10.1007/s10072-019-04167-wCrossRefPubMed

13.

Kataoka H, Sugie K (2020) Serum adiponectin levels between patients with Parkinson’s disease and those with PSP. Neurol Sci 41(5):1–7. https://doi.org/10.1007/s10072-019-04216-4CrossRef

14.

Lashuel H, Overk C, Oueslati A, Masliah E (2012) The many faces of α-synuclein: from structure and toxicity to therapeutic target. Nat Rev Neurosci 14(1):38–48. https://doi.org/10.1038/nrn3406CrossRef

15.

Lee E, Woo M, Moon P, Baek M, Choi I, Kim W, Junn E, Kim HS (2010) α-Synuclein activates microglia by inducing the expressions of matrix metalloproteinases and the subsequent activation of protease-activated receptor-1. J Immunol 185(1):615–623. https://doi.org/10.4049/jimmunol.0903480CrossRefPubMed

16.

Rojanathammanee L, Murphy E, Combs C (2011) Expression of mutant alpha-synuclein modulates microglial phenotype in vitro. J Neuroinflammation 8(1):44. https://doi.org/10.1186/1742-2094-8-44CrossRefPubMedPubMedCentral

17.

Chakrabarty P, Ceballos-Diaz C, Beccard A, Janus C, Dickson D, Golde T, Das P (2010) IFN-γ promotes complement expression and attenuates amyloid plaque deposition in amyloid β precursor protein transgenic mice. J Immunol 184(9):5333–5343. https://doi.org/10.4049/jimmunol.0903382CrossRefPubMed

18.

Porras G, Li Q, Bezard E (2011) Modeling Parkinson’s disease in primates: the MPTP model. Cold Spring Harb Perspect Med 2(3):a009308. https://doi.org/10.1101/cshperspect.a009308CrossRef

19.

Park J, Lim CS, Seo H, Park CA, Zhuo M, Kaang BK, Lee K (2015) Pain perception in acute model mice of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mol Pain 11:28. https://doi.org/10.1186/2Fs12990-015-0026-1CrossRefPubMedPubMedCentral

20.

Hou L, Zhou X, Zhang C, Wang K, Liu X, Che Y, Sun F, Huihua L, Wang Q, Zhang D, Honge JS (2017) NADPH oxidase-derived H2O2 mediates the regulatory effects of microglia on astrogliosis in experimental models of Parkinson’s disease. Redox Biol 12:162–170. https://doi.org/10.1016/j.redox.2017.02.016CrossRefPubMedPubMedCentral

21.

Winblad B, Amouyel P, Andrieu S, Ballard C, Brayne C, Brodaty H, Cedazo-Minguez A, Dubois B, Edvardsson D, Feldman H, Fratiglioni L, Frisoni GB, Gauthier S, Georges J, Graff C, Iqbal K, Jessen F, Johansson G, Jönsson L, Kivipelto M, Knapp M, Mangialasche F, Melis R, Nordberg A, Rikkert MO, Qiu C, Sakmar TP, Scheltens P, Schneider LS, Sperling R, Tjernberg LO, Waldemar G, Wimo A, Zetterberg H (2016) Defeating Alzheimer’s disease and other dementias: a priority for European science and society. Lancet Neurol 15(5):455–532. https://doi.org/10.1016/S1474-4422(16)00062-4CrossRefPubMed

22.

Palmqvist S, Schöll M, Strandberg O, Mattsson N, Stomrud E, Zetterberg H, Blennow K, Landau S, Jagust W, Hansson O (2017) Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity. Nat Commun 8(1):1214. https://doi.org/10.1038/s41467-017-01150-xCrossRefPubMedPubMedCentral

23.

Prokop S, Miller K, Heppner F (2013) Microglia actions in Alzheimer’s disease. Acta Neuropathol 126(4):461–477. https://doi.org/10.1007/s00401-013-1182-xCrossRefPubMed

24.

Fiebich BL, Batista CRA, Saliba SW, Yousif NM, de Oliveira ACP (2018) Role of microglia TLRs in neurodegeneration. Front Cell Neurosci 12:329. https://doi.org/10.3389/fncel.2018.00329CrossRefPubMedPubMedCentral

25.

Parajuli B, Sonobe Y, Horiuchi H, Takeuchi H, Mizuno T, Suzumura A (2013) Oligomeric amyloid β induces IL-1β processing via production of ROS: implication in Alzheimer’s disease. Cell Death Disease 4(12):e975. https://doi.org/10.1038/cddis.2013.503CrossRefPubMedPubMedCentral

26.

Kim C, Ho D, Suk J, You S, Michael S, Kang J, Joong Lee S, Masliah E, Hwang D, Lee HJ, Lee SJ (2013) Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat Commun 4(1):1562. https://doi.org/10.1038/ncomms2534CrossRefPubMed

27.

Krasemann S, Madore C, Cialic R, Baufeld C, Calcagno N, El Fatimy R, Beckers L, O’Loughlin E, Xu Y, Fanek Z, Greco DJ, Smithm ST, Tweet G, Humulock Z, Zrzavy T, Conde-Sanroman P, Gacias M, Weng Z, Butovsky O (2017) The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47(3):566–581. https://doi.org/10.1016/j.immuni.2017.08.008CrossRefPubMedPubMedCentral

28.

Yi ZQ, Zhao P, Zhang H, Shi Y, Shi H, Zhong J, Pan P (2020) Theory of mind in Alzheimer’s disease and amnestic mild cognitive impairment: a meta-analysis. Neur Sci 41(5):1–13. https://doi.org/10.1007/s10072-019-04215-5CrossRef

29.

Martinez B, Peplow PV (2019) Amelioration of Alzheimer’s disease pathology and cognitive deficits by immunomodulatory agents in animal models of Alzheimer’s disease. Neural Regen Res 14(7):1158–1176. https://doi.org/10.4103/1673-5374.251192CrossRefPubMedPubMedCentral

30.

Mawuenyega K, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris J, Yarasheski KE, Bateman RJ (2010) Decreased clearance of CNS β-amyloid in Alzheimer’s disease. Science 330(6012):1774. https://doi.org/10.1126/science.1197623CrossRefPubMedPubMedCentral

31.

Kraft A, Hu X, Yoon H, Yan P, Xiao Q, Wang Y, Gil SC, Brown J, Wilhelmsson U, Restivo JL, Cirrito JR, Holtzman DM, Kim J, Pekny M, Lee JM (2013) Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice. FASEB J 27(1):187–198. https://doi.org/10.1096/fj.12-208660CrossRefPubMedPubMedCentral

32.

Kawahara K, Suenobu M, Yoshida A, Koga K, Hyodo A, Ohtsuka H, Kuniyasu A, Tamamaki N, Sugimoto Y, Nakayama H (2012) Intracerebral microinjection of interleukin-4/interleukin-13 reduces β-amyloid accumulation in the ipsilateral side and improves cognitive deficits in young amyloid precursor protein 23 mice. Neuroscience 207:243–260. https://doi.org/10.1016/j.neuroscience.2012.01.049CrossRefPubMed

33.

Kiyota T, Ingraham K, Swan R, Jacobsen M, Andrews S, Ikezu T (2011) AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP+PS1 mice. Gene Ther 19(7):724–733. https://doi.org/10.1038/gt.2011.126CrossRefPubMedPubMedCentral

34.

Luo X, Chen S (2012) The changing phenotype of microglia from homeostasis to disease. Transl Neurodegener 1(1):9. https://doi.org/10.1186/2047-9158-1-9CrossRefPubMedPubMedCentral

35.

Tang Y, Li T, Li J, Yang J, Liu H, Zhang X, Le W (2013) Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson’s disease. Cell Death Differ 21(3):369–380. https://doi.org/10.1038/cdd.2013.159CrossRefPubMedPubMedCentral

36.

Lee D, Ruiz C, Lebson L, Selenica M, Rizer J, Hunt J, Rojiani R, Reid P, Kammath S, Nash K (2013) Aging enhances classical activation but mitigates alternative activation in the central nervous system. Neurobiol Aging 34(6):1610–1620. https://doi.org/10.1016/j.neurobiolaging.2012.12.014CrossRefPubMedPubMedCentral

37.

Saakyan SV, Myakoshina EB, Krichevskaya GI, Slepova OS, Panteleeva OG, Andryushin AE, Khoroshilova LP, Zakharova GP (2016) Testing patients with uveal melanoma for herpesvirus infections. Voprosy Virusologii 61(6):284–287. https://doi.org/10.18821/0507-4088-2016-61-6-284-287CrossRef

38.

Lauro C, Catalano M, Trettel F, Limatola C (2015) Fractalkine in the nervous system: neuroprotective or neurotoxic molecule? Ann NY Acad Sci 1351(1):141–148. https://doi.org/10.1111/nyas.12805CrossRefPubMed

39.

Poniatowski Ł, Wojdasiewicz P, Krawczyk M, Szukiewicz D, Gasik R, Kubaszewski Ł, Kurkowska-Jastrzębska I (2016) Analysis of the role of CX3CL1 (Fractalkine) and its receptor CX3CR1 in traumatic brain and spinal cord injury: insight into recent advances in actions of neurochemokine agents. Mol Neurobiol 54(3):2167–2188. https://doi.org/10.1007/s12035-016-9787-4CrossRefPubMedPubMedCentral

40.

Mecca C, Giambanco I, Donato R, Arcuri C (2018) Microglia and aging: the role of the TREM2–DAP12 and CX3CL1-CX3CR1 axes. Int J Mol Sci 19(1):318. https://doi.org/10.3390/ijms19010318CrossRefPubMedCentral

41.

Sanchez-Guajardo V, Barnum C, Tansey M, Romero-Ramos M (2013) Neuroimmunological processes in Parkinson’s disease and their relation to α-synuclein: microglia as the referee between neuronal processes and peripheral immunity. ASN Neuro 5(2):AN20120066. https://doi.org/10.1042/2FAN20120066CrossRef

Titel: The role of microglia in the development of neurodegeneration
verfasst von: Aigul R. Saitgareeva
Kirill V. Bulygin
Ilgiz F. Gareev
Ozal A. Beylerli
Leila R. Akhmadeeva
Publikationsdatum: 26.05.2020
Verlag: Springer International Publishing
Erschienen in: Neurological Sciences / Ausgabe 12/2020
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-020-04468-5

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

18.04.2024 | Arterielle Hypertonie | Nachrichten

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

The role of microglia in the development of neurodegeneration

Abstract

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

Manche Gestagene können das Risiko für Meningeome erhöhen

Parkinson: Größere Studie bestätigt Genauigkeit von Hauttest

Update Neurologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2020

“Spreading the word of the master”: the contribution of Italian physicians in the early dissemination of Jean-Martin Charcot’s theories

New-onset anosmia and taste distortion: see beyond COVID-19

Neurological manifestations of COVID-19: a systematic review and meta-analysis of proportions

The stroke mothership model survived during COVID-19 era: an observational single-center study in Emilia-Romagna, Italy

A waves in electroneurography: differential diagnosis with other late responses

MicroRNAs in amyotrophic lateral sclerosis: from pathogenetic involvement to diagnostic biomarker and therapeutic agent development

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

Manche Gestagene können das Risiko für Meningeome erhöhen

Parkinson: Größere Studie bestätigt Genauigkeit von Hauttest

Update Neurologie