The Mechanism of Motor Neuron Degeneration through Dysfunction of Ubiquitin-Proteasome Systems. Mus musculus strain:C57BL/6J

The progressive accumulation of damaged proteins is a hallmark of aging-related diseases, including neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). The ubiquitin-proteasome system (UPS) is crucial for protein degradation, and its dysfunction leads to the collapse of proteostasis, resulting in cell death. We have previously discovered that a decline in UPS function within motor neurons contributes to sporadic ALS pathologies, characterized by progressive motor neuron loss, protein accumulation, and glial activation. However, the specific mechanisms by which UPS dysfunction induces cell damage, including cell death and aggregation, remain poorly understood. The goal of this study is to use Psmc4 conditional knockout mice, which have a proteasome deficiency specific to motor neurons, to elucidate the mechanism of motor neuron degeneration caused by UPS dysfunction, thereby clarifying the pathophysiological mechanisms of ALS.