Expression of Mutant Ubiquitin and Proteostasis Impairment in Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex Brains. Issue 8 (6th August 2020)

• Record Type: Journal Article
• Authors: Verheijen, Bert M; Morimoto, Satoru; Sasaki, Ryogen; Oyanagi, Kiyomitsu; Kokubo, Yasumasa; Kuzuhara, Shigeki; van Leeuwen, Fred W
• Is Part Of: Journal of neuropathology and experimental neurology. Volume 79:Issue 8(2020)
• Page Start: 902
• Page End: 907
• Publication Date: 2020-08-06
• Subjects: Autophagy -- Kii ALS/PDC -- Protein aggregation -- Protein quality control -- Tauopathy -- UBB+1 -- Ubiquitin-proteasome system -- Unfolded protein response; Neurology -- Diseases -- Periodicals; Neurology -- Diseases -- Physiopathology -- Periodicals; 616.8047
• DOI: 10.1093/jnen/nlaa056
• Languages: English
• ISSNs: 0022-3069

Abstract

Abstract: 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 autophagy-lysosome pathway, in postmortem brain tissue from a number of Kii 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.