Mitochondrial Dysfunction, Neurogenesis, and Epigenetics: Putative Implications for Amyotrophic Lateral Sclerosis Neurodegeneration and Treatment

Author(s)

Calio, Michele Longoni ^[1] ; Henriques, Elisandra ^[2] ; Siena, Amanda ^[2] ; Bertoncini, Clelia Rejane Antonio ^[3] ; Gil-Mohapel, Joana ^{[4, 5]} ; Rosenstock, Tatiana Rosado ^{[4, 5]}

Affiliation

^[1] Univ Fed Sao Paulo, Dept Physiol, Sao Paulo - Brazil

^[2] Santa Casa Sao Paulo Sch Med Sci, Dept Physiol Sci, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Ctr Dev Expt Models Med & Biol, CEDEME, Sao Paulo - Brazil

^[4] Univ Victoria, Div Med Sci, Fac Med, Victoria, BC - Canada

^[5] Univ British Columbia, Isl Med Program, Victoria, BC - Canada

• Document type: Review article
• Source: FRONTIERS IN NEUROSCIENCE; v. 14, JUL 15 2020.
• Web of Science Citations: 0

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive and devastating multifactorial neurodegenerative disorder. Although the pathogenesis of ALS is still not completely understood, numerous studies suggest that mitochondrial deregulation may be implicated in its onset and progression. Interestingly, mitochondrial deregulation has also been associated with changes in neural stem cells (NSC) proliferation, differentiation, and migration. In this review, we highlight the importance of mitochondrial function for neurogenesis, and how both processes are correlated and may contribute to the pathogenesis of ALS; we have focused primarily on preclinical data from animal models of ALS, since to date no studies have evaluated this link using human samples. As there is currently no cure and no effective therapy to counteract ALS, we have also discussed how improving neurogenic function by epigenetic modulation could benefit ALS. In support of this hypothesis, changes in histone deacetylation can alter mitochondrial function, which in turn might ameliorate cellular proliferation as well as neuronal differentiation and migration. We propose that modulation of epigenetics, mitochondrial function, and neurogenesis might provide new hope for ALS patients, and studies exploring these new territories are warranted in the near future. (AU)

• FAPESP's process: 15/02041-1 - The role of lysine(K)-deacetylases on mitochondrial disorders's neuroprotection: perspectives of epigenetic therapy for amyotrophic lateral sclerosis and schizophrenia
• Grantee: Tatiana Rosado Rosenstock
• Support Opportunities: Research Grants - Young Investigators Grants