Premotor parkinsonism models

Parkinsonism Relat Disord. 2014 Jan:20 Suppl 1:S17-9. doi: 10.1016/S1353-8020(13)70007-5.


Aside from motor symptoms, Parkinson's disease is associated with a number of non-motor symptoms arising many years before motor signs. The most prevalent and predictive premotor symptoms include olfactory dysfunction, REM sleep behaviour disorder (RBD) and constipation. Several studies in toxin- or gene-based models have specifically investigated these non-motor signs in a premotor context. Altered olfactory discrimination has been reproduced both in toxin- and in gene-based models, and genetic models may also reproduce the underlying pathophysiological mechanisms. Sleep alterations have also been demonstrated, mostly in toxin-based models, and RBD-like features can be demonstrated in non-human primates. Gastrointestinal dysfunction and associated enteric pathology are reproduced both in toxin and genetic models displaying reduced colonic motility and enteric α-synuclein accumulation. This review describes the main premotor symptoms that are recapitulated both in toxin- and in gene-based models, their relevance to the human disease, and their potential to understand the underlying mechanisms of early symptoms and disease progression.

Keywords: Constipation; Non-human primate; Olfactory dysfunction; REM sleep behaviour disorder; Rodent models.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Disease Progression
  • Gastrointestinal Diseases / complications
  • Humans
  • Olfaction Disorders / complications
  • Parkinsonian Disorders / complications*
  • Parkinsonian Disorders / diagnosis*
  • Prodromal Symptoms*
  • Sleep Wake Disorders / complications