The gut may act as the starting point of Parkinson's Disease pathology with spread toward the central nervous system

[Emily]

http://www.wjgnet.com/esps/DownLoad...&FilePath=Pub\10.3748\v22\i25\WJG-22-5742.pdf

World J Gastroenterol 2016 July 7; 22(25): 5742-5752
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
? 2016 Baishideng Publishing Group Inc. All rights reserved.
Gut dysfunction in Parkinson's disease
Adreesh Mukherjee, Atanu Biswas, Shyamal Kumar Das

 

[Emily]

http://www.nature.com/nrneurol/journ....2015.197.html

Pathogenesis of Parkinson disease— the gut–-brain axis and environmental factors

• Lisa Klingelhoefer[SUP]1[/SUP][SUP], [/SUP]
• Heinz Reichmann[SUP]1[/SUP][SUP], [/SUP]

Nature Reviews Neurology 11,625–636 (2015) doi:10.1038/nrneurol.2015.197 Published online 27 October 2015

• Parkinson disease (PD) follows a defined clinical pattern, and a range of nonmotor symptoms precede the motor phase. The predominant early nonmotor manifestations are olfactory impairment and constipation. The pathology that accompanies these symptoms is consistent with the Braak staging system: α-synuclein in the dorsal motor nucleus of the vagus nerve, the olfactory bulb, the enteric nervous system (ENS) and the submandibular gland, each of which is a gateway to the environment. The neuropathological process that leads to PD seems to start in the ENS or the olfactory bulb and spreads via rostrocranial transmission to the substantia nigra and further into the CNS, raising the intriguing possibility that environmental substances can trigger pathogenesis. Evidence from epidemiological studies and animal models supports this hypothesis. For example, in mice, intragastric administration of the pesticide rotenone can almost completely reproduce the typical pathological and clinical features of PD. In this Review, we present clinical and pathological evidence to support the hypothesis that PD starts in the gut and spreads via trans-synaptic cell-to-cell transfer of pathology through the sympathetic and parasympathetic nervous systems to the substantia nigra and the CNS. We also consider how environmental factors might trigger pathogenesis, and the potential for therapeutically targeting the mechanisms of these initial stages.