Amyotrophic Lateral Sclerosis Modifiers in Drosophila Reveal the Phospholipase D Pathway as a Potential Therapeutic Target.

ABSTRACT: Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a devastating neurodegenerative disorder lacking effective treatments. ALS pathology is linked to mutations in >20 different genes indicating a complex underlying genetic architecture that is effectively unknown. Here, in an attempt to identify genes and pathways for potential therapeutic intervention and explore the genetic circuitry underlying Drosophila models of ALS, we carry out two independent genome-wide screens for modifiers of degenerative phenotypes associated with the expression of transgenic constructs carrying familial ALS-causing alleles of FUS (hFUS^R521C) and TDP-43 (hTDP-43^M337V). We uncover a complex array of genes affecting either or both of the two strains, and in

SUBMITTER: Kankel MW 

PROVIDER: S-EPMC7337071 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature