Expression of Mutant Ubiquitin and Proteostasis Impairment in Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex Brains.
| Autor: | Verheijen BM; From the Departments of Translational Neuroscience and Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Morimoto S; Department of Oncologic Pathology, Mie University, Graduate School of Medicine., Sasaki R; Department of Neurology, Kuwana City Medical Center, Mie., Oyanagi K; Division of Neuropathology, Department of Brain Disease Research, Shinshu University School of Medicine, Matsumoto, Nagano., Kokubo Y; Kii ALS/PDC Research Center, Mie University Graduate School of Regional Innovation Studies., Kuzuhara S; Neurology and Medicine, School of Nursing, Suzuka University of Medical Science, Mie, Japan., van Leeuwen FW; Department of Neuroscience, Maastricht University, Maastricht, The Netherlands. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of neuropathology and experimental neurology [J Neuropathol Exp Neurol] 2020 Aug 01; Vol. 79 (8), pp. 902-907. |
| DOI: | 10.1093/jnen/nlaa056 |
| Abstrakt: | 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. (© 2020 American Association of Neuropathologists, Inc.) |
| Databáze: | MEDLINE |
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