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 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.
Original language | English |
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Pages (from-to) | 902-907 |
Number of pages | 6 |
Journal | Journal of Neuropathology and Experimental Neurology |
Volume | 79 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 2020 |
Keywords
- Autophagy
- Kii ALS/PDC
- Protein aggregation
- Protein quality control
- Tauopathy
- UBB+1
- Ubiquitin-proteasome system
- Unfolded protein response
- NEURODEGENERATIVE DISORDERS
- ENDEMIC DISEASE
- PARKINSONISM
- SCLEROSIS
- TAU
- ACCUMULATION
- PENINSULA
- PROTEIN
- JAPAN
- ALZHEIMERS