Protein kinetics of superoxide dismutase-1 in familial and sporadic amyotrophic lateral sclerosis.

ABSTRACT:

Objective

Accumulation of misfolded superoxide dismutase-1 (SOD1) is a pathological hallmark of SOD1-related amyotrophic lateral sclerosis (ALS) and is observed in sporadic ALS where its role in pathogenesis is controversial. Understanding in vivo protein kinetics may clarify how SOD1 influences neurodegeneration and inform optimal dosing for therapies that lower SOD1 transcripts.

Methods

We employed stable isotope labeling paired with mass spectrometry to evaluate in vivo protein kinetics and concentration of soluble SOD1 in cerebrospinal fluid (CSF) of SOD1 mutation carriers, sporadic ALS participants and controls. A deaminated SOD1 peptide, SDGPVKV, that correlates with protein stability was also measured.

Results

In participants with heterozygous SOD1^A5V

SUBMITTER: Ly CV 

PROVIDER: S-EPMC10270254 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature