Mutational and transcriptional profiling of cuproptosis-associated genes in amyotrophic lateral sclerosis

In summary, our scrutiny of genetic variants within genes implicated in Cu metabolism and their cell type-specific transcriptomic alterations within the primary motor cortex has unveiled preliminary evidence supporting the intriguing association 108 between cuproptosis genes and ALS. These findings highlighted the yet unclarified roles of Cu in disease pathogenesis, holding the promise of meaningful mechanistic insights and potential therapeutic avenues. Given the dual associations of mitochondrial Cu overload and deficiency with aggregation-induced cell death, future research endeavors may focus on elucidating the specific cellular states that modulate Cu-induced cytotoxicity, leveraging animal models and induced pluripotent stem cell (iPSC)-derived motor neurons from ALS patients to further advance our understanding of cuproptosis in ALS