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Alpha-Synuclein-induced Kv4 channelopathy in mouse vagal motoneurons drives nonmotor parkinsonian symptoms


Chiu, WH and Kovacheva, L and Musgrove, RE and Arien-Zakay, H and Koprich, JB and Brotchie, J and Yaka, R and Ben-Zvi, D and Hanani, M and Roeper, J and Goldberg, JA, Alpha-Synuclein-induced Kv4 channelopathy in mouse vagal motoneurons drives nonmotor parkinsonian symptoms, Science Advances, 7, (11) Article eabd3994. ISSN 2375-2548 (2021) [Refereed Article]

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DOI: doi:10.1126/sciadv.abd3994


No disease-modifying therapy is currently available for Parkinson's disease (PD), the second most common neurodegenerative disease. The long nonmotor prodromal phase of PD is a window of opportunity for early detection and intervention. However, we lack the pathophysiological understanding to develop selective biomarkers and interventions. By using a mutant a-synuclein selective-overexpression mouse model of prodromal PD, we identified a cell-autonomous selective Kv4 channelopathy in dorsal motor nucleus of the vagus (DMV) neurons. This functional remodeling of intact DMV neurons leads to impaired pacemaker function in vitro and in vivo, which, in turn, reduces gastrointestinal motility, a common early symptom of prodromal PD. We identify a chain of events from a-synuclein via a biophysical dysfunction of a specific neuronal population to a clinically relevant prodromal symptom. These findings will facilitate the rational design of clinical biomarkers to identify people at risk for developing PD.

Item Details

Item Type:Refereed Article
Keywords:Parkinson's disease; neurodegenerative disease; clinical biomarkers
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Musgrove, RE (Dr Ruth Musgrove)
ID Code:152637
Year Published:2021
Web of Science® Times Cited:4
Deposited By:Research Performance and Analysis
Deposited On:2022-08-22
Last Modified:2022-09-13

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