Acid Ceramidase Depletion Impairs Neuronal Survival and Induces Morphological Defects in Neurites Associated with Altered Gene Transcription and Sphingolipid Content.

ABSTRACT: The ASAH1 gene encodes acid ceramidase (AC), an enzyme that is implicated in the metabolism of ceramide (Cer). Mutations in the ASAH1 gene cause two different disorders, Farber disease (FD), a rare lysosomal storage disorder, and a rare form of spinal muscular atrophy combined with progressive myoclonic epilepsy (SMA-PME). In the absence of human in vitro neuronal disease models and to gain mechanistic insights into pathological effects of ASAH1 deficiency, we established and characterized a stable ASAH1 knockdown (ASAH1^KD) SH-SY5Y cell line. ASAH1^KD cells displayed reduced proliferation due to elevated apoptosis and G1/S cell cycle arrest. Distribution of LAMP1-positive lysosomes towards the cell periphery and significantly s

SUBMITTER: Kyriakou K 

PROVIDER: S-EPMC7084529 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature