The relationship between cholesterol and Parkinson’s disease

Human studies
 ↓ Cholesterol synthesisCholesterol biosynthesis is decreased in fibroblasts from patients with PD owing to reduced HMG-CoA reductase activity.[81]
 ↓ Serum cholesterol levelsThe serum levels of total cholesterol, LDL-cholesterol, VLDL-cholesterol, and triglyceride are reduced in patients with PD.[8385]
Low serum total or LDL-cholesterol level is associated with higher occurrence of PD, faster clinical progression or more severe symptoms in PD patients.[86, 87]
Low total cholesterol level is associated with faster clinical progression.[88]
Low serum LDL-cholesterol level is associated with more severe symptoms in PD patients.[89]
 ↓ Plasma ApoA-I levelLow plasma levels of ApoA-I are found in PD.[95]
Low plasma levels of ApoA-I are associated with age at onset and motor severity in early PD patients.[95, 96]
 ↓ Plasma 24-HC[128] levelThe level of 24-HC is decreased in the plasma of patients with PD.[105, 106]
 ↑ CSF 24-HC level24-HC level is increased in the CSF of patient with PD.[107]
 ↓ Cholesterol proportion in membrane lipid raftsThe proportion of cholesterol in membrane lipid rafts appeared to be reduced in PD brains.[109]
Model studies
 MPTP modelHypercholesterolemia exacerbate MPTP-induced reduction of striatal dopamine and dopaminergic neurons in the substantia nigra with motor behavioral depreciation in mice.[111]
The high cholesterol level incorporated into differentiated SH-SY5Y cells worsens dopaminergic neuronal survivability.[112]
 α-SynucleinCholesterol mediates the interaction of oligomeric α-synuclein with the cell membrane.[123]
Elevated levels of oxidized cholesterol metabolites in Lewy body disease brains accelerate α-synuclein fibrilization.[124]
α-Synuclein aggregation increases at low concentrations of ApoE.[125]
27-HC increases α-synuclein protein levels through proteasomal inhibition in human dopaminergic neurons.[126]
Cholesterol levels is increased in the brain of α-synuclein transgenic mice.[121]
Brain cholesterol, cholesteryl ester, and triacylglycerol mass are increased in α-synuclein KO mice.[122]
 ParkinTotal cholesterol level is increased and the membrane fluidity is decreased in parkin deficient MEF cells, causing dysregulation of lipid rafts-dependent endocytosis[128]
The increase in serum cholesterol level by high fat diet is less pronounced in parkin KO mice.[129]
 PINK1PINK1 is associated with lipid rafts in in vitro models.[137]
 DJ-1DJ-1 deficiency in astrocytes causes decrease in cellular cholesterol level, increase in membrane fluidity, and decrease in lipid rafts-dependent endocytosis.[131, 132]
Cholesterol supplementation rescues the synaptic endocytic defects observed in DJ-1-deficient neurons.[133]
Expression of LDLR mRNA and protein were reduced in DJ-1-knockdown cells and DJ-1 KO mice.[134]
 LRRK2The plasma cholesterol level is elevated in LRRK2 KO rats.[135]
 UCH-L1UCH-L1 is associated with lipid rafts in in vitro models.[139]

CSF, cerebrospinal fluid; HC, hydroxycholesterol; HMG-CoA, β-Hydroxy β-methylglutaryl-CoA; KO, knock out; MEF, mouse embryonic fibroblast; LDL, low-density lipoprotein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; PD, Parkinson’s disease; VLDL, very low-density lipoprotein.

Experimental Neurobiology 2019;28:554~567
© Exp Neurobiol