Integrative organelle-based functional proteomics in ARSACS-focus on bioenergetics and autophagy

ABSTRACT: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an inherited neurodegenerative disease characterized by early-onset spasticity in the lower limbs, axonal-demyelinating sensorimotor peripheral neuropathy, and cerebellar ataxia. Our understanding of the genetic basis, protein function and disease mechanisms of ARSACS have been only partially explored. The integrative use of organelle-based quantitative proteomics and whole genome analysis proposed in this study, allowed identifying affected pathways, upstream regulators, and disease and biological functions related to ARSACS, with a motivation for setting improved, early diagnostic strategies and to offer alternative treatment options in a rare condition without the cure. Our results deepen the evidence for the impairment of autophagy and mitochondrial dysfunction in SACS knockout lysosomes and mitochondrial compartment, anticipating putative candidate biomarkers related to organelle damage.

INSTRUMENT(S): Synapt G2-S HDMS

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Maciej Lalowski   Filippo M. Santorelli  

PROVIDER: MSV000088592 | MassIVE | Mon Dec 20 08:44:00 GMT 2021

SECONDARY ACCESSION(S): PXD030541

REPOSITORIES: MassIVE