TGF-β1: ALS Astrocytes’ Secret Sauce?

Inflammation, in moderation? Increased levels of TGF-β1, secreted by astrocytes, may fuel the progression of ALS by blocking the ability of key immune cells to help heal injured motor neurons and promote their survival (see April 2015, May 2015 news). [Courtesy of Endo et al., 2015. Cell Reports.]

Astrocytes may destroy motor neurons in at least some forms of ALS. But how these key cells kill motor neurons remains unknown.

Now, a research team led by Harvard University’s Qiao Zhou in Massachusetts report that reactive astrocytes may promote the destruction of motor neurons in co-culture by secreting TGF-β1 (Tripathi et al., 2017). The study found that increased levels of TGF-β1, produced by wild-type or SOD1 G93A reactive astrocytes isolated from mice, induced the cytoplasmic aggregation of key proteins, impaired autophagy and reduced the survival of human embryonic stem cell-derived motor neurons.

The study is published on June 29 in Stem Cell Reports.

The findings build on previous work led by Nagoya University’s Koji Yamanaka in Japan, which found that the progression of ALS may be mediated by a TGF-β1-mediated mechanism (see April 2015 news; Endo et al., 2015).

Together, the results suggest that reducing excess levels of TGF-β1 may be a potential approach to slow progression of the disease.

References

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. Reactive Astrocytes Promote ALS-like Degeneration and Intracellular Protein Aggregation in Human Motor Neurons by Disrupting Autophagy through TGF-β1. Stem Cell Reports. 2017 Jun 29. [PubMed].

Endo F, Komine O, Fujimori-Tonou N, Katsuno M, Jin S, Watanabe S, Sobue G, Dezawa M, Wyss-Coray T, Yamanaka K. Astrocyte-Derived TGF-β1 Accelerates Disease Progression in ALS Mice by Interfering with the Neuroprotective Functions of Microglia and T Cells. Cell Rep. 2015 Apr 15 [PubMed].

Further Reading

Kunis G, Baruch K, Rosenzweig N, Kertser A, Miller O, Berkutzki T, Schwartz M. IFN-γ-dependent activation of the brain’s choroid plexus for CNS immune surveillance and repair. Brain. 2013 Nov;136(Pt 11):3427-40. [PubMed].

Kunis G, Baruch K, Miller O, Schwartz M. Immunization with a Myelin-Derived Antigen Activates the Brain’s Choroid Plexus for Recruitment of Immunoregulatory Cells to the CNS and Attenuates Disease Progression in a Mouse Model of ALS. J Neurosci. 2015 Apr 22;35(16):6381-93. [PubMed].

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