TY  - INPR
A1  - Chiu, Wei-Hua
A1  - Kovacheva, Lora
A1  - Musgrove, Ruth E.
A1  - Arien-Zakay, Hadar
A1  - Koprich, James B.
A1  - Brotchie, Jonathan M.
A1  - Yaka, Rami
A1  - Ben-Zvi, Danny
A1  - Hanani, Menachem
A1  - Roeper, Jochen
A1  - Goldberg, Joshua A.
T1  - α-Synuclein-induced Kv4 channelopathy in mouse vagal motoneurons causes non-motor parkinsonian symptoms
T2  - bioRxiv
N2  - No disease modifying therapy is currently available for Parkinson’s disease (PD), the second most common neurodegenerative disease. The long non-motor 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 developing a mutant α-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 which is a common, very early symptom of prodromal PD. We show for the first time a causal chain of events from α-synuclein via a biophysical dysfunction of specific neuronal populations to a clinically relevant prodromal symptom. These findings can facilitate the rational design of clinical biomarkers to identify people at risk for PD.
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72702
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-727023
IS  - 856070
ER  -