The gut-brain connection in the pathogenicity of Parkinson disease: Putative role of autophagy

• Published in: Neuroscience letters Vol. 753; p. 135865
• Main Authors: Kakoty, Violina, K C, Sarathlal, Dubey, Sunil Kumar, Yang, Chih Hao, Kesharwani, Prashant, Taliyan, Rajeev
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 14.05.2021
• Subjects: Autophagy; Gut; Parkinson disease; Trehalose; Vagus nerve; Parkinson disease; Vagus nerve; Trehalose; Autophagy; Gut
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2021.135865

•Parkinson Disease (PD) is a neurodegenerative movement disorder with certain autonomous dysfunctions.•Misfolded alpha-synuclein (α-syn) may progress towards the brain via the vagus nerve at a very early stage.•Enhancement in the process of autophagy to flush out misfolded α-syn has been of particular interest in PD research.•Trehalose enters into the brain from the gut and possibly contribute towards ameliorating PD pathology. Parkinson disease (PD) is a progressive movement functionality disorder resulting in tremor and inability to execute voluntary functions combined with the preponderant non-motor disturbances encompassing constipation and gastrointestinal irritation. Despite continued research, the pathogenesis of PD is not yet clear. The available class of drugs for effective symptomatic management of PD includes a combination of levodopa and carbidopa. In recent past, the link between gut with PD has been explored. According to recent preclinical evidence, pathogens such as virus or bacterium may initiate entry into the gut via the nasal cavity that may aggravate lewy pathology in the gut that eventually propagates and progresses towards the brain via the vagus nerve resulting in the prodromal non-motor symptoms. Additionally, experimental evidence also suggests that alpha-synuclein misfolding commences at a very early stage in the gut and is transported via the vagus nerve prior to seeding PD pathology in the brain. However, this progression and resultant deterioration of the neurones can effectively be altered by an autophagy inducer, Trehalose, although the mechanism behind it is still enigmatic. Hence, this review will mainly focus on analysing the basic components of the gut that might be responsible for aggravating lewy pathology, the mediator(s) responsible for transmission of PD pathology from gut to brain and the important role of trehalose in ameliorating gut dysbiosis related PD complications that would eventually pave the way for therapeutic management of PD.