Non-CNS pathogenic origin of Parkinson's disease

J Neurol. 2017 Sep;264(9):2027-2030. doi: 10.1007/s00415-017-8588-7. Epub 2017 Aug 14.


The gut with its variety of microbiota may serve as an etiological origin of diseases. Gut microbes may also play a role in the pathogenesis of diseases beyond their simple nutritional maintenance and support. For example, gut protein aggregation, possibly aided by microbes as well as nasal influences, might be linked to disease that may move to the brain through the vagus nerve. To this end, Braak has offered a "dual-hit" hypothesis that proposes a novel etiology for Parkinson's disease (PD). The hypothesis places the initial origin of the disease in the nose and the gastrointestinal tract (GI) after infection by an unknown pathogen that could aggregate in the gut and then eventually spread to the brain via the autonomic plexuses. Gut health functioning, therefore, may affect brain status and behavior. A protein known as alpha-synuclein accumulates in brains of people with Parkinson's disease that is also present in the GI before the onset of motor symptoms. Therefore, the stomach, previously thought to be a stable mechanism throughout life, might explain some etiological origins of disease. Finally, the vagus nerve of the autonomic system that extends from the brain to the abdomen and exercises both sympathetic and parasympathetic roles might be associated with PD diagnosis along with Lewy body influences.

Keywords: Alpha-synuclein; Braak’s “dual-hit” hypothesis; Gut microbes; Parkinson’s disease; Peripheral α-synucleinopathy; Vagus nerve.

MeSH terms

  • Gastrointestinal Microbiome / physiology*
  • Gastrointestinal Tract* / metabolism
  • Gastrointestinal Tract* / microbiology
  • Gastrointestinal Tract* / physiopathology
  • Humans
  • Models, Biological
  • Nasal Mucosa* / metabolism
  • Nose* / immunology
  • Nose* / microbiology
  • Parkinson Disease / microbiology*
  • Parkinson Disease / pathology*
  • Vagus Nerve / physiology