期刊
SCIENCE ADVANCES
卷 7, 期 11, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abd3994
关键词
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资金
- German-Israeli Foundation for Scientific Research and Development [I-1294-418.13/2015]
- German Research Foundation Collaborative Research Center 815 Redox Signaling program
- European Research Council [646880]
- European Research Council (ERC) [646880] Funding Source: European Research Council (ERC)
Research has identified a cell-autonomous selective Kv4 channelopathy in PD prodromal mice, leading to impaired gastrointestinal motility, serving as a potential clinical biomarker for early detection of PD.
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 alpha-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 alpha-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.
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