Cholesterol Metabolism in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets

Mol Neurobiol. 2021 May;58(5):2183-2201. doi: 10.1007/s12035-020-02232-6. Epub 2021 Jan 7.

Abstract

Cholesterol is an indispensable component of the cell membrane and plays vital roles in critical physiological processes. Brain cholesterol accounts for a large portion of total cholesterol in the human body, and its content must be tightly regulated to ensure normal brain function. Disorders of cholesterol metabolism in the brain are linked to neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and other atypical cognitive deficits that arise at old age. However, the specific role of cholesterol metabolism disorder in the pathogenesis of neurodegenerative diseases has not been fully elucidated. Statins that are a class of lipid-lowering drugs have been reported to have a positive effect on neurodegenerative diseases. Herein, we reviewed the physiological and pathological conditions of cholesterol metabolism and discussed the possible mechanisms of cholesterol metabolism and statin therapy in neurodegenerative diseases.

Keywords: Alzheimer’s disease (AD); Cholesterol metabolism; Neurodegenerative diseases; Parkinson’s disease (PD); Statin therapy.

Publication types

  • Review

MeSH terms

  • Brain / metabolism*
  • Cholesterol / metabolism*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / physiology
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism*

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol