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

Violina Kakoty, Sarathlal K C, Sunil Kumar Dubey, Chih Hao Yang, Prashant Kesharwani, Rajeev Taliyan

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish
Article number135865
JournalNeuroscience Letters
Volume753
DOIs
Publication statusPublished - May 14 2021

Keywords

  • Autophagy
  • Gut
  • Parkinson disease
  • Trehalose
  • Vagus nerve

ASJC Scopus subject areas

  • Neuroscience(all)

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