Therapies modulating insulin resistance in Parkinson's disease: A cross talk

Neurosci Lett. 2021 Apr 1:749:135754. doi: 10.1016/j.neulet.2021.135754. Epub 2021 Feb 18.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder linked with aging and primarily involves dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc). The deregulation of genes associated with T2D has been demonstrated by proteomic research on Parkinson's symptoms patients. Various common pathways likely to link neurodegenerative mechanisms of PD include abnormal mitochondrial function, inflammation, apoptosis/autophagy and insulin signalling/glucose metabolism in T2DM. Several pathway components including phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt), glycogen synthase kinase-3 beta (GSK-3β) and nuclear factor kappa B (NF-κB) impairment is observed in PD. Numerous novel targets are being pursued in preclinical and clinical trials that target metabolic dysfunction in PD; that elevate insulin signaling pathways in dopaminergic neurons, and show improvement in motor and cognitive measures and produce significant neuroprotective effects in PD patients.

Keywords: Cognitive impairment; Dopaminergic neuronal loss; Insulin signaling; Parkinson’s disease; Type 2 diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism*
  • Humans
  • Inflammation / metabolism
  • Insulin / metabolism*
  • Insulin Resistance / physiology*
  • Neuroprotective Agents / pharmacology
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism*
  • Phosphatidylinositol 3-Kinase / metabolism
  • Signal Transduction / drug effects

Substances

  • Insulin
  • Neuroprotective Agents
  • Phosphatidylinositol 3-Kinase