The relationship between cholesterol and Parkinson’s disease
Findings | References | |
---|---|---|
Human studies | ||
↓ Cholesterol synthesis | Cholesterol biosynthesis is decreased in fibroblasts from patients with PD owing to reduced HMG-CoA reductase activity. | [ |
↓ Serum cholesterol levels | The serum levels of total cholesterol, LDL-cholesterol, VLDL-cholesterol, and triglyceride are reduced in patients with PD. | [ |
Low serum total or LDL-cholesterol level is associated with higher occurrence of PD, faster clinical progression or more severe symptoms in PD patients. | [ | |
Low total cholesterol level is associated with faster clinical progression. | [ | |
Low serum LDL-cholesterol level is associated with more severe symptoms in PD patients. | [ | |
↓ Plasma ApoA-I level | Low plasma levels of ApoA-I are found in PD. | [ |
Low plasma levels of ApoA-I are associated with age at onset and motor severity in early PD patients. | [ | |
↓ Plasma 24-HC[ | The level of 24-HC is decreased in the plasma of patients with PD. | [ |
↑ CSF 24-HC level | 24-HC level is increased in the CSF of patient with PD. | [ |
↓ Cholesterol proportion in membrane lipid rafts | The proportion of cholesterol in membrane lipid rafts appeared to be reduced in PD brains. | [ |
Model studies | ||
MPTP model | Hypercholesterolemia exacerbate MPTP-induced reduction of striatal dopamine and dopaminergic neurons in the substantia nigra with motor behavioral depreciation in mice. | [ |
The high cholesterol level incorporated into differentiated SH-SY5Y cells worsens dopaminergic neuronal survivability. | [ | |
α-Synuclein | Cholesterol mediates the interaction of oligomeric α-synuclein with the cell membrane. | [ |
Elevated levels of oxidized cholesterol metabolites in Lewy body disease brains accelerate α-synuclein fibrilization. | [ | |
α-Synuclein aggregation increases at low concentrations of ApoE. | [ | |
27-HC increases α-synuclein protein levels through proteasomal inhibition in human dopaminergic neurons. | [ | |
Cholesterol levels is increased in the brain of α-synuclein transgenic mice. | [ | |
Brain cholesterol, cholesteryl ester, and triacylglycerol mass are increased in α-synuclein KO mice. | [ | |
Parkin | Total cholesterol level is increased and the membrane fluidity is decreased in parkin deficient MEF cells, causing dysregulation of lipid rafts-dependent endocytosis | [ |
The increase in serum cholesterol level by high fat diet is less pronounced in parkin KO mice. | [ | |
PINK1 | PINK1 is associated with lipid rafts in | [ |
DJ-1 | DJ-1 deficiency in astrocytes causes decrease in cellular cholesterol level, increase in membrane fluidity, and decrease in lipid rafts-dependent endocytosis. | [ |
Cholesterol supplementation rescues the synaptic endocytic defects observed in DJ-1-deficient neurons. | [ | |
Expression of LDLR mRNA and protein were reduced in DJ-1-knockdown cells and DJ-1 KO mice. | [ | |
LRRK2 | The plasma cholesterol level is elevated in LRRK2 KO rats. | [ |
UCH-L1 | UCH-L1 is associated with lipid rafts in | [ |
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.