The potential role of cholesterol in Parkinson’s disease neuropathology: perpetrator or victim.

Publication date: Jul 10, 2023

Parkinson’s disease (PD) is a neurodegenerative disease characterized by deposition of α-synuclein and aggregation of Lewy bodies. Cholesterol is involved with PD neuropathology in bidirectional ways that could be protective or harmful. Thus, the objective of the present review was to verify the potential role of cholesterol in PD neuropathology. Deregulation of ion channels and receptors induced by cholesterol alteration suggests a possible mechanism for the neuroprotective effects of cholesterol against PD development. However, high serum cholesterol level increases PD risk indirectly by 27-hydroxycholesterol which induces oxidative stress, inflammation, and apoptosis. Besides, hypercholesterolemia triggers the accumulation of cholesterol in macrophages and immune cells leading to the release of pro-inflammatory cytokines with progression of neuroinflammation subsequently. Additionally, cholesterol increases aggregation of α-synuclein and induces degeneration of dopaminergic neurons (DN) in the substantia nigra (SN). Hypercholesterolemia may lead to cellular Ca overload causing synaptic and the development of neurodegeneration. In conclusion, cholesterol has bidirectional effects on PD neuropathology and might be protective or harmful.

Concepts Keywords
Hypercholesterolemia Cholesterol
Nigra Parkinson’s disease
Parkinson α-synuclein


Type Source Name
drug DRUGBANK Cholesterol
disease MESH neurodegenerative disease
disease MESH oxidative stress
disease MESH inflammation
pathway KEGG Apoptosis
disease MESH hypercholesterolemia
disease MESH neuroinflammation

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