A Possible Role for HMG-CoA Reductase Inhibitors and Its Association with HMGCR Genetic Variation in Parkinson's Disease

Int J Mol Sci. 2021 Nov 11;22(22):12198. doi: 10.3390/ijms222212198.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease characterised by both motor- and non-motor symptoms, including cognitive impairment. The aetiopathogenesis of PD, as well as its protective and susceptibility factors, are still elusive. Neuroprotective effects of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors-statins-via both cholesterol-dependent and independent mechanisms have been shown in animal and cell culture models. However, the available data provide conflicting results on the role of statin treatment in PD patients. Moreover, cholesterol is a vital component for brain functions and may be considered as protective against PD. We present possible statin effects on PD under the hypothesis that they may depend on the HMG-CoA reductase gene (HMGCR) variability, such as haplotype 7, which was shown to affect cholesterol synthesis and statin treatment outcome, diminishing possible neuroprotection associated with HMG-CoA reductase inhibitors administration. Statins are among the most prescribed groups of drugs. Thus, it seems important to review the available data in the context of their possible neuroprotective effects in PD, and the HMG-CoA reductase gene's genetic variability.

Keywords: HMG-CoA reductase inhibitors; Parkinson’s disease; genetic polymorphisms; neuroprotection; statins.

Publication types

  • Review

MeSH terms

  • Genetic Variation*
  • Humans
  • Hydroxymethylglutaryl CoA Reductases* / genetics
  • Hydroxymethylglutaryl CoA Reductases* / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Neuroprotective Agents / therapeutic use*
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / enzymology
  • Parkinson Disease* / genetics

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Neuroprotective Agents
  • HMGCR protein, human
  • Hydroxymethylglutaryl CoA Reductases