Neurodegenerative Diseases: Unraveling the Heterogeneity of Astrocytes.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Astrocytes*/metabolism ; Astrocytes*/pathology ; Neurodegenerative Diseases*/metabolism ; Neurodegenerative Diseases*/pathology; Humans ; Animals ; Phenotype

The astrocyte population, around 50% of human brain cells, plays a crucial role in maintaining the overall health and functionality of the central nervous system (CNS). Astrocytes are vital in orchestrating neuronal development by releasing synaptogenic molecules and eliminating excessive synapses. They also modulate neuronal excitability and contribute to CNS homeostasis, promoting neuronal survival by clearance of neurotransmitters, transporting metabolites, and secreting trophic factors. Astrocytes are highly heterogeneous and respond to CNS injuries and diseases through a process known as reactive astrogliosis, which can contribute to both inflammation and its resolution. Recent evidence has revealed remarkable alterations in astrocyte transcriptomes in response to several diseases, identifying at least two distinct phenotypes called A1 or neurotoxic and A2 or neuroprotective astrocytes. However, due to the vast heterogeneity of these cells, it is limited to classify them into only two phenotypes. This review explores the various physiological and pathophysiological roles, potential markers, and pathways that might be activated in different astrocytic phenotypes. Furthermore, we discuss the astrocyte heterogeneity in the main neurodegenerative diseases and identify potential therapeutic strategies. Understanding the underlying mechanisms in the differentiation and imbalance of the astrocytic population will allow the identification of specific biomarkers and timely therapeutic approaches in various neurodegenerative diseases.

Neuron. 2014 Jul 2;83(1):27-49. (PMID: 24991953)
Int J Mol Sci. 2022 Mar 18;23(6):. (PMID: 35328727)
J Cell Physiol. 2008 Oct;217(1):215-27. (PMID: 18521822)
FASEB J. 2019 Oct;33(10):10859-10871. (PMID: 31266356)
Neurochem Res. 2019 Jun;44(6):1410-1424. (PMID: 30661228)
Cold Spring Harb Perspect Biol. 2017 Jul 5;9(7):. (PMID: 28062563)
Exp Neurol. 2009 Nov;220(1):183-90. (PMID: 19716366)
J Neuroimmunol. 2020 Jun 23;346:577284. (PMID: 32652366)
Front Pharmacol. 2023 Mar 29;14:1111925. (PMID: 37063271)
Eur J Neurol. 2019 Jan;26(1):27-40. (PMID: 30300457)
Biochem Pharmacol. 2021 Jun;188:114578. (PMID: 33895160)
Front Immunol. 2023 Oct 23;14:1254586. (PMID: 37936690)
Front Cell Neurosci. 2022 Aug 17;16:896172. (PMID: 36060277)
Glia. 2023 Feb;71(2):229-244. (PMID: 36063073)
Mol Pharmacol. 2018 Oct;94(4):1174-1186. (PMID: 30111648)
Neurochem Int. 2021 May;145:104956. (PMID: 33503465)
J Neuroinflammation. 2016 May 04;13(1):99. (PMID: 27143001)
Alzheimers Res Ther. 2017 Nov 09;9(1):89. (PMID: 29121998)
J Neurosci. 2019 Mar 27;39(13):2441-2458. (PMID: 30700530)
Neurochem Res. 2020 Jun;45(6):1298-1305. (PMID: 32006215)
J Cell Physiol. 2018 Jan;234(1):904-914. (PMID: 30076715)
Neurobiol Dis. 2011 Feb;41(2):508-27. (PMID: 21056667)
Arch Med Res. 2018 Feb;49(2):130-131. (PMID: 29861329)
Neuroimmunomodulation. 2021;28(2):82-89. (PMID: 33735898)
Aging (Albany NY). 2018 Jun 23;10(6):1474-1488. (PMID: 29936495)
Cell Death Dis. 2020 May 15;11(5):377. (PMID: 32415059)
Nat Immunol. 2007 Mar;8(3):247-56. (PMID: 17277779)
J Neuroinflammation. 2020 Nov 22;17(1):348. (PMID: 33222695)
Cell Cycle. 2019 Nov;18(21):3010-3029. (PMID: 31530090)
Neurosci Res. 2022 Nov;184:38-46. (PMID: 35940437)
Expert Opin Ther Targets. 2019 Oct;23(10):865-882. (PMID: 31580163)
Mol Neurobiol. 2019 Sep;56(9):5971-5986. (PMID: 30701416)
Nat Commun. 2022 Nov 2;13(1):6581. (PMID: 36323693)
J Neurosci. 2010 Oct 20;30(42):14008-19. (PMID: 20962222)
Front Mol Neurosci. 2019 Oct 25;12:258. (PMID: 31708741)
ACS Nano. 2020 Jan 28;14(1):360-371. (PMID: 31887011)
Front Cell Neurosci. 2021 Nov 17;15:755955. (PMID: 34867201)
Cell Death Differ. 2012 May;19(5):779-87. (PMID: 22095276)
Acta Neuropathol Commun. 2023 Mar 13;11(1):42. (PMID: 36915214)
Nature. 2017 Jan 26;541(7638):481-487. (PMID: 28099414)
J Immunol Res. 2020 Nov 16;2020:5907591. (PMID: 33282962)
J Neurosci. 2011 May 4;31(18):6627-38. (PMID: 21543591)
Int J Mol Sci. 2020 Jun 13;21(12):. (PMID: 32545828)
Cell Death Discov. 2019 Apr 3;5:85. (PMID: 30962951)
Adv Sci (Weinh). 2022 Jun;9(18):e2104640. (PMID: 35488520)
Int Immunopharmacol. 2017 Sep;50:353-360. (PMID: 28753520)
J Neuroimmunol. 2014 Sep 15;274(1-2):53-61. (PMID: 25005117)
Brain. 2017 Feb;140(2):399-413. (PMID: 28007993)
Cell Physiol Biochem. 2016;38(3):859-70. (PMID: 26910882)
Pharmacology. 2020;105(1-2):3-8. (PMID: 31537002)
Front Cell Neurosci. 2021 Jun 21;15:654284. (PMID: 34234647)
Nat Med. 2018 Mar;24(3):326-337. (PMID: 29400711)
Nature. 2017 Nov 8;551(7679):192-197. (PMID: 29120426)
BMC Neurosci. 2022 Nov 27;23(1):70. (PMID: 36437451)
Front Immunol. 2020 Jul 08;11:1024. (PMID: 32733433)
Nature. 2021 Nov;599(7883):102-107. (PMID: 34616039)
Oxid Med Cell Longev. 2022 Sep 1;2022:3800004. (PMID: 36092158)
Int J Mol Sci. 2021 Oct 28;22(21):. (PMID: 34769132)
Mult Scler Relat Disord. 2022 Apr;60:103749. (PMID: 35339008)
Neuropsychopharmacology. 2023 Jan;48(1):21-36. (PMID: 35577914)
Neuron. 2008 Nov 6;60(3):430-40. (PMID: 18995817)
Neuroscience. 2020 Feb 1;426:189-200. (PMID: 31866556)
Acta Neuropathol Commun. 2021 Apr 26;9(1):78. (PMID: 33902708)
Nutrients. 2022 Aug 03;14(15):. (PMID: 35956355)
Biomedicines. 2023 Jan 07;11(1):. (PMID: 36672665)
Front Immunol. 2022 Feb 28;13:845011. (PMID: 35296090)
J Neurosci. 2008 Dec 10;28(50):13574-81. (PMID: 19074031)
Glia. 2020 Dec;68(12):2693-2704. (PMID: 32619303)
Pract Neurol. 2022 Feb;22(1):32-41. (PMID: 34413240)
Front Pharmacol. 2021 Nov 15;12:760186. (PMID: 34867376)
Trends Neurosci. 2020 Dec;43(12):965-979. (PMID: 33127097)
J Neuroinflammation. 2010 Oct 11;7:62. (PMID: 20937129)
Int J Mol Sci. 2022 Sep 27;23(19):. (PMID: 36232716)
Nat Immunol. 2007 Dec;8(12):1390-7. (PMID: 17994024)
CNS Neurosci Ther. 2019 Jun;25(6):665-673. (PMID: 30929313)
Biomolecules. 2021 Sep 14;11(9):. (PMID: 34572572)
Front Immunol. 2020 Apr 08;11:635. (PMID: 32322257)
Pain Physician. 2022 Nov;25(8):E1199-E1210. (PMID: 36375190)
J Mol Histol. 2022 Apr;53(2):333-346. (PMID: 35031895)
Ann Neurol. 2013 Nov;74(5):709-20. (PMID: 23818336)
Cell Rep. 2019 Nov 19;29(8):2384-2397.e5. (PMID: 31747607)
Glia. 2017 Jan;65(1):50-61. (PMID: 27615381)
J Neurosci. 2012 May 2;32(18):6391-410. (PMID: 22553043)
BMJ Open. 2019 Oct 7;9(10):e029740. (PMID: 31594876)
Exp Neurol. 2022 Feb;348:113943. (PMID: 34863998)
Nat Rev Dis Primers. 2017 Mar 23;3:17013. (PMID: 28332488)
J Clin Invest. 2003 Jan;111(1):3-10. (PMID: 12511579)
Front Aging Neurosci. 2017 Jun 19;9:193. (PMID: 28674491)
Neurologia (Engl Ed). 2020 Jul - Aug;35(6):400-408. (PMID: 28958395)
Neurochem Int. 2021 Sep;148:105080. (PMID: 34048845)
Glia. 2015 Dec;63(12):2260-73. (PMID: 26200799)
Neurosci Bull. 2024 Apr;40(4):483-499. (PMID: 37979054)
Brain Commun. 2019 Oct 21;1(1):fcz028. (PMID: 32954268)
Nat Aging. 2022 Sep;2(9):837-850. (PMID: 37118504)
Nat Commun. 2014 Nov 19;5:5422. (PMID: 25406732)
J Clin Med. 2021 Feb 19;10(4):. (PMID: 33669652)
J Neurosci. 2011 Sep 21;31(38):13412-9. (PMID: 21940434)
Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):E197-205. (PMID: 22167804)
Immunity. 2017 Jun 20;46(6):957-967. (PMID: 28636962)
Front Pharmacol. 2021 Jan 13;11:565700. (PMID: 33519431)
Arch Pharm Res. 2019 May;42(5):416-425. (PMID: 30830660)
Asian Pac J Trop Med. 2015 Jan;8(1):64-7. (PMID: 25901927)
J Neurosci. 2016 Jan 13;36(2):577-89. (PMID: 26758846)
Lancet. 2021 Sep 25;398(10306):1184-1194. (PMID: 34175020)
Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):2012-2017. (PMID: 28167760)
Immunol Lett. 2023 Jul;259:1-8. (PMID: 37244460)
Int J Mol Sci. 2020 May 20;21(10):. (PMID: 32443829)
Neuron. 2020 Nov 25;108(4):608-622. (PMID: 32898475)
Nat Med. 2023 Jul;29(7):1775-1781. (PMID: 37248300)
Neuron. 2020 Aug 5;107(3):436-453.e12. (PMID: 32485136)
Acta Neuropathol. 2020 Sep;140(3):359-375. (PMID: 32710244)
EMBO J. 2018 Aug 15;37(16):. (PMID: 29875132)
Nat Rev Neurosci. 2020 Aug;21(8):401-415. (PMID: 32555340)
Trends Immunol. 2020 Sep;41(9):758-770. (PMID: 32819810)
Front Neurosci. 2019 Jun 04;13:569. (PMID: 31213977)
J Exp Med. 2012 Mar 12;209(3):521-35. (PMID: 22393127)
Sci Transl Med. 2019 Oct 16;11(514):. (PMID: 31619545)
Int J Mol Sci. 2021 Nov 19;22(22):. (PMID: 34830387)
Cell Rep. 2020 Nov 3;33(5):108271. (PMID: 33147455)
JAMA Neurol. 2022 Mar 01;79(3):261-270. (PMID: 35099506)
J Neuroinflammation. 2009 Apr 28;6:14. (PMID: 19400960)
Neural Regen Res. 2021 Sep;16(9):1702-1710. (PMID: 33510058)
Nat Commun. 2018 Apr 16;9(1):1479. (PMID: 29662056)
Brain Sci. 2023 Jun 28;13(7):. (PMID: 37508938)
Front Cell Neurosci. 2017 Feb 13;11:24. (PMID: 28243193)
Int J Mol Sci. 2023 Feb 27;24(5):. (PMID: 36902058)
Annu Rev Immunol. 2017 Apr 26;35:441-468. (PMID: 28226226)
Nat Neurosci. 2021 Mar;24(3):312-325. (PMID: 33589835)
Food Chem Toxicol. 2022 Jun;164:113017. (PMID: 35452770)
J Neurosci. 2020 Dec 9;40(50):9751-9771. (PMID: 33158962)
Cold Spring Harb Perspect Med. 2019 Jan 2;9(1):. (PMID: 29358321)
Dement Geriatr Cogn Disord. 2009;27(3):286-91. (PMID: 19246914)
J Neuropathol Exp Neurol. 2013 Jun;72(6):462-71. (PMID: 23656989)
Mult Scler. 2020 Dec;26(14):1816-1821. (PMID: 33174475)
Glia. 2004 Oct;48(1):76-84. (PMID: 15326617)
Front Immunol. 2019 Jun 04;10:1265. (PMID: 31275302)
Cell Death Dis. 2020 Jun 1;11(6):411. (PMID: 32483154)
Brain Res. 2021 May 1;1758:147341. (PMID: 33548270)
Biochem Pharmacol. 2018 May;151:245-251. (PMID: 29305854)
Annu Rev Neurosci. 2019 Jul 8;42:187-207. (PMID: 31283899)
Front Immunol. 2022 Feb 08;13:824411. (PMID: 35211120)
Behav Brain Res. 2021 Sep 24;414:113481. (PMID: 34302876)
Adv Exp Med Biol. 2018;1049:1-28. (PMID: 29427096)
J Parkinsons Dis. 2018;8(s1):S3-S8. (PMID: 30584159)
Curr Opin Neurobiol. 2022 Jun;74:102550. (PMID: 35544965)
Biochem Biophys Res Commun. 2020 Nov 12;532(3):475-481. (PMID: 32892947)
Biomed Rep. 2015 Mar;3(2):141-146. (PMID: 25798237)
Nat Med. 2018 Jul;24(7):931-938. (PMID: 29892066)
J Mol Neurosci. 2019 Oct;69(2):324-332. (PMID: 31327154)
Brain Behav Immun. 2020 Jul;87:804-819. (PMID: 32194232)
Mol Cell Neurosci. 2022 Sep;122:103758. (PMID: 35868484)
Biochem Biophys Res Commun. 2022 Apr 30;602:1-7. (PMID: 35247698)
J Immunol. 2014 Jul 1;193(1):139-49. (PMID: 24860191)
Oncotarget. 2017 May 31;8(31):50329-50330. (PMID: 28881562)
Int J Mol Sci. 2023 Jul 28;24(15):. (PMID: 37569510)
Glia. 2010 May;58(7):831-8. (PMID: 20140958)
Curr Neuropharmacol. 2022;20(6):1116-1143. (PMID: 34852742)
Am J Pathol. 2002 May;160(5):1583-7. (PMID: 12000710)
Acta Neuropathol Commun. 2017 Nov 29;5(1):89. (PMID: 29187256)
Commun Biol. 2022 Mar 29;5(1):282. (PMID: 35351973)
Neuron. 2015 Jan 7;85(1):101-115. (PMID: 25533482)
Front Neurosci. 2019 May 03;13:429. (PMID: 31130839)
Aging (Albany NY). 2021 Sep 29;13(18):21812-21813. (PMID: 34587119)
Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):16975-80. (PMID: 24082147)
Neuroscience. 2016 Aug 25;330:205-18. (PMID: 27241943)
FEBS J. 2018 Oct;285(19):3576-3590. (PMID: 29323772)
PLoS One. 2011;6(11):e26674. (PMID: 22125600)
Neurotherapeutics. 2021 Jul;18(3):1834-1848. (PMID: 34260042)
Brain Behav Immun. 2021 Jan;91:740-755. (PMID: 33039660)
Cell Metab. 2022 Aug 2;34(8):1104-1120.e8. (PMID: 35738259)
Int J Mol Sci. 2020 Aug 20;21(17):. (PMID: 32825423)
Front Cell Neurosci. 2023 Mar 27;17:1125412. (PMID: 37051111)
Mol Cell Endocrinol. 2022 Feb 15;542:111529. (PMID: 34906628)
J Neuroinflammation. 2020 Aug 11;17(1):235. (PMID: 32782006)
Cold Spring Harb Perspect Med. 2018 Sep 4;8(9):. (PMID: 29358317)
Signal Transduct Target Ther. 2017;2:. (PMID: 29158945)
Acta Neuropathol. 2019 May;137(5):757-783. (PMID: 30847559)
Exp Mol Pathol. 2023 Feb;129:104846. (PMID: 36436571)
Acta Neuropathol Commun. 2020 Apr 22;8(1):56. (PMID: 32321590)
Nat Neurosci. 2020 Jun;23(6):701-706. (PMID: 32341542)
J Neuroinflammation. 2020 Jul 14;17(1):211. (PMID: 32665021)
Curr Opin Pharmacol. 2022 Aug;65:102261. (PMID: 35809402)
Exp Neurol. 2022 Feb;348:113947. (PMID: 34902359)
J Neuroinflammation. 2021 Jun 3;18(1):124. (PMID: 34082772)
Science. 1996 May 3;272(5262):735-8. (PMID: 8614837)
Cell Rep. 2022 Oct 25;41(4):111532. (PMID: 36288697)
Front Aging Neurosci. 2022 Oct 10;14:937486. (PMID: 36299608)
Int J Mol Sci. 2023 Feb 09;24(4):. (PMID: 36834929)

(IA205423, IN206322, IN219623) UNAM-PAPIIT; A1-S-10064 and 319433. the Consejo Nacional de Humanidades, Ciencias y Tecnologías (CONAHCYT)

Keywords: Alzheimer’s disease; Huntington’s disease; Parkinson’s disease; multiple sclerosis; neurotoxic and neuroprotective astrocytes

Date Created: 20240619 Date Completed: 20240619 Latest Revision: 20250121

20250122

PMC11172252

10.3390/cells13110921

38891053