Proteome Homeostasis Dysfunction: A Unifying Principle in ALS Pathogenesis.

We present a hypothesis that proposes all genetic lesions associated with ALS (including in mRNA-binding proteins) cause widespread imbalance to an already metastable proteome. The impact of such dysfunction is felt across the entire proteome and is not restricted to a small subset of proteins. Proteome imbalance may cause functional defects, such as excitability alterations, and eventually cell death. While this idea is a unifying principle for all of ALS, we propose that stratification will appear that might dictate the efficacy of therapeutics based on the proteostasis network. PMID: 32353332 [PubMed - in process]
Source: Trends in Neurosciences - Category: Neuroscience Authors: Tags: Trends Neurosci Source Type: research