Experimental Neurobiology

Table 2

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.	[81]
↓ Serum cholesterol levels	The serum levels of total cholesterol, LDL-cholesterol, VLDL-cholesterol, and triglyceride are reduced in patients with PD.	[83–85]
	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 level	Low 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] level	The level of 24-HC is decreased in the plasma of patients with PD.	[105, 106]
↑ CSF 24-HC level	24-HC level is increased in the CSF of patient with PD.	[107]
↓ Cholesterol proportion in membrane lipid rafts	The proportion of cholesterol in membrane lipid rafts appeared to be reduced in PD brains.	[109]
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.	[111]
	The high cholesterol level incorporated into differentiated SH-SY5Y cells worsens dopaminergic neuronal survivability.	[112]
α-Synuclein	Cholesterol 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]
Parkin	Total 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]
PINK1	PINK1 is associated with lipid rafts in in vitro models.	[137]
DJ-1	DJ-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]
LRRK2	The plasma cholesterol level is elevated in LRRK2 KO rats.	[135]
UCH-L1	UCH-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.

Exp Neurobiol 2019;28:554~567 https://doi.org/10.5607/en.2019.28.5.554