ER stress links aging to sporadic ALS

Most cases of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS) have no familial history, being considered sporadic [1]. Aging is the main risk factor to the occurrence of such conditions, which are collectively termed protein misfolding disorders (PMDs) due to the accumulation of aggregated proteins in the brain [2]. Proteostasis impairment is one of the hallmarks of aging, which may contribute to the accumulation of misfolded proteins in disease states. Thus, it is fundamental to understand how age-related alterations to the proteostasis network drive formation of toxic protein species and downstream pathogenic cascades. We reason that profiling the protein misfolding and aggregation process during aging at the biochemical level may uncover molecular pathways underlying disease etiology