Proteome Homeostasis Dysfunction: A Unifying Principle in ALS Pathogenesis.

摘要: Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease but currently has no effective treatment. Growing evidence suggests that proteome homeostasis underlies ALS pathogenesis. Protein production, trafficking, and degradation all shape proteome. We present a hypothesis proposes genetic lesions associated with (including in mRNA-binding proteins) cause widespread imbalance to an already metastable The impact of such dysfunction felt across entire not restricted small subset proteins. Proteome may functional defects, as excitability alterations, eventually cell death. While this idea unifying principle for ALS, we propose stratification will appear might dictate efficacy therapeutics based on proteostasis network.