The multi-dimensional roles of astrocytes in ALS - PubMed

Review

The multi-dimensional roles of astrocytes in ALS

Koji Yamanaka et al. Neurosci Res. 2018 Jan.

Free article

Abstract

Despite significant progress in understanding the molecular and genetic aspects of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, the precise and comprehensive pathomechanisms remain largely unknown. In addition to motor neuron involvement, recent studies using cellular and animal models of ALS indicate that there is a complex interplay between motor neurons and neighboring non-neuronal cells, such as astrocytes, in non-cell autonomous neurodegeneration. Astrocytes are key homeostatic cells that play numerous supportive roles in maintaining the brain environment. In neurodegenerative diseases such as ALS, astrocytes change their shape and molecular expression patterns and are referred to as reactive or activated astrocytes. Reactive astrocytes in ALS lose their beneficial functions and gain detrimental roles. In addition, interactions between motor neurons and astrocytes are impaired in ALS. In this review, we summarize growing evidence that astrocytes are critically involved in the survival and demise of motor neurons through several key molecules and cascades in astrocytes in both sporadic and inherited ALS. These observations strongly suggest that astrocytes have multi-dimensional roles in disease and are a viable therapeutic target for ALS.

Keywords: ALS; Astrocyte; Neuroinflammation; SOD1; TDP-43.

Similar articles

• Role and Therapeutic Potential of Astrocytes in Amyotrophic Lateral Sclerosis.

  Pehar M, Harlan BA, Killoy KM, Vargas MR. Pehar M, et al. Curr Pharm Des. 2017;23(33):5010-5021. doi: 10.2174/1381612823666170622095802. Curr Pharm Des. 2017. PMID: 28641533 Free PMC article. Review.

• Distinct responses of neurons and astrocytes to TDP-43 proteinopathy in amyotrophic lateral sclerosis.

  Smethurst P, Risse E, Tyzack GE, Mitchell JS, Taha DM, Chen YR, Newcombe J, Collinge J, Sidle K, Patani R. Smethurst P, et al. Brain. 2020 Feb 1;143(2):430-440. doi: 10.1093/brain/awz419. Brain. 2020. PMID: 32040555 Free PMC article.

• Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes.

  Gorter RP, Stephenson J, Nutma E, Anink J, de Jonge JC, Baron W, Jahreiβ MC, Belien JAM, van Noort JM, Mijnsbergen C, Aronica E, Amor S. Gorter RP, et al. Neuropathol Appl Neurobiol. 2019 Aug;45(5):459-475. doi: 10.1111/nan.12525. Epub 2018 Nov 23. Neuropathol Appl Neurobiol. 2019. PMID: 30346063 Free PMC article.

• Reactive Astrocytes Promote ALS-like Degeneration and Intracellular Protein Aggregation in Human Motor Neurons by Disrupting Autophagy through TGF-β1.

  Tripathi P, Rodriguez-Muela N, Klim JR, de Boer AS, Agrawal S, Sandoe J, Lopes CS, Ogliari KS, Williams LA, Shear M, Rubin LL, Eggan K, Zhou Q. Tripathi P, et al. Stem Cell Reports. 2017 Aug 8;9(2):667-680. doi: 10.1016/j.stemcr.2017.06.008. Epub 2017 Jul 14. Stem Cell Reports. 2017. PMID: 28712846 Free PMC article.

• Astrocytes Pathology in ALS: A Potential Therapeutic Target?

  Johann S. Johann S. Curr Pharm Des. 2017;23(33):5022-5036. doi: 10.2174/1381612823666170615110856. Curr Pharm Des. 2017. PMID: 28619000 Review.

Cited by

• Secreted Metabolome of ALS-Related hSOD1(G93A) Primary Cultures of Myocytes and Implications for Myogenesis.

  Stella R, Bonadio RS, Cagnin S, Andreotti R, Massimino ML, Bertoli A, Peggion C. Stella R, et al. Cells. 2023 Nov 30;12(23):2751. doi: 10.3390/cells12232751. Cells. 2023. PMID: 38067180 Free PMC article.

• Elevated Cerebrospinal Fluid Proteins and Albumin Determine a Poor Prognosis for Spinal Amyotrophic Lateral Sclerosis.

  Assialioui A, Domínguez R, Ferrer I, Andrés-Benito P, Povedano M. Assialioui A, et al. Int J Mol Sci. 2022 Sep 21;23(19):11063. doi: 10.3390/ijms231911063. Int J Mol Sci. 2022. PMID: 36232365 Free PMC article.

• Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial Inflammation.

  Hashimoto Y, Yamasaki R, Ko S, Matsuo E, Kobayakawa Y, Masaki K, Matsuse D, Isobe N. Hashimoto Y, et al. Int J Mol Sci. 2022 Dec 16;23(24):16046. doi: 10.3390/ijms232416046. Int J Mol Sci. 2022. PMID: 36555685 Free PMC article.

• Endothelin-1, over-expressed in SOD1^G93A mice, aggravates injury of NSC34-hSOD1G93A cells through complicated molecular mechanism revealed by quantitative proteomics analysis.

  Zhang Y, Chen L, Li Z, Li D, Wu Y, Guo Y. Zhang Y, et al. Front Cell Neurosci. 2022 Dec 1;16:1069617. doi: 10.3389/fncel.2022.1069617. eCollection 2022. Front Cell Neurosci. 2022. PMID: 36531135 Free PMC article.

• Blood Level of Glial Fibrillary Acidic Protein (GFAP) Does not Correlate With Disease Progression in a Rat Model of Familial ALS (SOD1^G93A Transgenic).

  Jeffrey J, D'Cunha H, Suzuki M. Jeffrey J, et al. Front Neurol. 2018 Nov 14;9:954. doi: 10.3389/fneur.2018.00954. eCollection 2018. Front Neurol. 2018. PMID: 30487774 Free PMC article.

Publication types

MeSH terms

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • scite Smart Citations

• Medical

  • MedlinePlus Health Information

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Miscellaneous

  • NCI CPTAC Assay Portal