Dysregulation of the autophagy-endolysosomal system in amyotrophic lateral sclerosis and frontotemporal dementia

Shinji Hadano

Molecular Neuropathobiology Laboratory, Department of Physiology, Tokai University School of Medicine

Recent studies have revealed that ALS and FTD are genetically, pathologically, and clinically related spectrum diseases, sharing an increasing number of causative and/or associated genes.　Among the complex toxic pathways, the disruption of homeostatic protein turnover and degradation has recently gained prominence.　These processes are exclusively mediated by evolutionarily conserved proteolytic systems:the ubiquitin-proteasome system （UPS） and the autophagy-endolysosomal system （APELS）.　The UPS plays a major role in the selective degradation of ubiquitinated proteins by the proteasome, while the APELS is responsible for the lysosome-mediated elimination of damaged proteins and organelles.　This review covers the APELS comprehensively and explores its dysfunction in ALS-FTD spectrum.

Address correspondence to Dr. Shinji Hadano, Molecular Neuropathobiology Laboratory, Department of Physiology, Tokai University School of Medicine （143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan）