所属：大阪大学大学院医学系研究科神経内科学

概要：Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes motor neuron degeneration. However, the mechanisms underlying the selective vulnerability and involvement of non-motor neuron cells in ALS remain unclear. To investigate ALS pathology at the cellular level, we conducted a multiome (single-nucleus RNA sequencing and assay for transposase-accessible chromatin using sequencing) analysis using the motor cortex and spinal cord of patients with ALS and control individuals. Our results revealed significant gene expression changes in spinal motor neurons. We also identified enhanced glutamate signaling in spinal motor neurons as a prominent feature. By integrating genome-wide association study data, we identified ALS-associated SNPs in regulatory regions, suggesting cell-type-specific enrichment of risk, especially in microglia. These findings suggest that changes in spinal motor neurons and their surrounding environment, including glutamate signaling, may be involved in ALS pathology and provide valuable resources for future research on the mechanisms and potential therapeutic targets.