期刊
ACTA NEUROPATHOLOGICA
卷 135, 期 1, 页码 1-12出版社
SPRINGER
DOI: 10.1007/s00401-017-1777-8
关键词
Parkinson's disease; Enteric nervous system; Gut; Alpha-synuclein; Vagus nerve; Dorsal motor nucleus of the vagus
资金
- France Parkinson
- Institut de France
- CECAP (Comite d'Entente et de Coordination des Associations de Parkinsoniens)
- FFGP (Federation francaise des groupements parkinsoniens)
- Parkinsoniens de Vendee
- US National Institute on Aging [P30 AG19610]
- National Institute of Neurological Disorders and Stroke [U24 NS072026]
- Arizona Department of Health Services [211002]
- Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]
- Michael J. Fox Foundation for Parkinson's Research
- NATIONAL INSTITUTE ON AGING [P30AG019610] Funding Source: NIH RePORTER
Parkinson's disease (PD) is pathologically characterized by the presence of intraneuronal inclusions, termed Lewy bodies and Lewy neurites, whose main component is alpha-synuclein. Based on the topographic distribution of Lewy bodies and neurites established after autopsy from PD patients, Braak and coworkers hypothesized that PD pathology may start in the gastrointestinal tract then spread through the vagus nerve to the brain. This hypothesis has been reinforced by the discovery that alpha-synuclein may be capable of spreading transcellularly, thereby providing a mechanistic basis for Braak's hypothesis. This 'gut to brain' scenario has ignited heated debates within the movement disorders community and prompted a large number of studies in both humans and animals. Here, we review the arguments for and against the gut as the origin of PD. We conclude that the human autopsy evidence does not support the hypothesis and that it is too early to draw any definitive conclusions. We discuss how this issue might be further addressed in future research.
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