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ID: ALA4627248

Journal: Bioorg Med Chem Lett

Title: Emerging small-molecule therapeutic approaches for amyotrophic lateral sclerosis and frontotemporal dementia.

Authors: Brown DG, Shorter J, Wobst HJ.

Abstract: Novel treatments are desperately needed for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In this review article, a survey of emerging small-molecule approaches for ALS and FTD therapies is provided. These approaches include targeting aberrant liquid-liquid phase separation and stress granule assembly, modulation of RNA-protein interactions, inhibition of TDP-43 phosphorylation, inhibition of poly(ADP-ribose) polymerases (PARP), RNA-targeting approaches to reduce RAN translation of dipeptide repeat proteins from repeat expansions of C9ORF72, and novel autophagy activation pathways. This review details the emerging small-molecule tools and leads in these areas, along with a critical perspective on the key challenges facing these opportunities.

CiteXplore: 31926785

DOI: 10.1016/j.bmcl.2019.126942