期刊
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
卷 79, 期 8, 页码 902-907出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/jnen/nlaa056
关键词
Autophagy; Kii ALS/PDC; Protein aggregation; Protein quality control; Tauopathy; UBB+1; Ubiquitin-proteasome system; Unfolded protein response
资金
- Mie Medical Fund
- Japan Intractable Diseases (Nanbyo) Research Foundation
- Japan Foundation for Neuroscience and Mental Health
- Research Committee of CNS Degenerative Diseases [H29-Nanchi-Ippan-085]
- Research Committee of Muro Disease (Kii ALS/PDC) [21210301]
- Ministry of Health, Labor and Welfare (MHLW), Japan through Ministry of Education, Culture, Sports, Science and Technology (MEXT) [25305030, 18KK0239, 17H01689, 18K07368, 15J03921, 19K17002, 15K09634, 18K07514]
- Collaborative Research Project of Brain Research Institute, Niigata University [2907, 201913]
- Japan Agency for Medical Research and Development, AMED [17ek0109139h0003]
- Grants-in-Aid for Scientific Research [18K07368, 15K09634, 15J03921, 18KK0239, 18K07514, 17H01689, 19K17002, 25305030] Funding Source: KAKEN
Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disorder that is endemic to the Kii peninsula of Japan. The disorder is clinically characterized by a variable combination of parkinsonism, dementia, and motor neuron symptoms. Despite extensive investigations, the etiology and pathogenesis of ALS/PDC remain unclear. At the neuropathological level, Kii ALS/PDC is characterized by neuronal loss and tau-dominant polyproteinopathy. Here, we report the accumulation of several proteins involved in protein homeostasis pathways, that is, the ubiquitin-proteasome system and the autophagylysosome pathway, in postmortem brain tissue from a number of Ku ALS/PDC cases (n = 4). Of particular interest is the presence of a mutant ubiquitin protein (UBB+1), which is indicative of disrupted ubiquitin homeostasis. The findings suggest that abnormal protein aggregation is linked to impaired protein homeostasis pathways in Kii ALS/PDC.
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