Cholesterol Metabolism in the Brain and Its Association with Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is the second most progressive neurodegenerative disorder of the aging population after Alzheimer’s disease (AD). Defects in the lysosomal systems and mitochondria have been suspected to cause the pathogenesis of PD. Nevertheless, the pathogenesis of PD remains obscure. Abnormal cholesterol metabolism is linked to numerous disorders, including atherosclerosis. The brain contains the highest level of cholesterol in the body and abnormal cholesterol metabolism links also many neurodegenerative disorders such as AD, PD, Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). The blood brain barrier effectively prevents uptake of lipoprotein-bound cholesterol from blood circulation. Accordingly, cholesterol level in the brain is independent from that in peripheral tissues. Because cholesterol metabolism in both peripheral tissue and the brain are quite different, cholesterol metabolism associated with neurodegeneration should be examined separately from that in peripheral tissues. Here, we review and compare cholesterol metabolism in the brain and peripheral tissues. Furthermore, the relationship between alterations in cholesterol metabolism and PD pathogenesis is reviewed.

Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons

“…It has been speculated that this loss underlies neuronal dysfunctions and the cognitive deficits present at this stage of life [ 41 , 42 , 43 ]. It has also been surmised that dysregulation of cholesterol metabolism is a major factor in neurological diseases accompanied by cognitive dysfunction, such as Alzheimer disease [ 44 , 45 ] (reviewed in [ 23 ]), Parkinson disease [ 46 ], and Huntington disease [ 47 ]. Epidemiological studies have suggested that individuals treated with statins have a lower risk of developing Alzheimer disease [ 25 , 28 , 48 ].…”

Soluble Epoxide Hydrolase Inhibition to Face Neuroinflammation in Parkinson’s Disease: A New Therapeutic Strategy

“…Finally, as mentioned, there are neurodegenerative diseases for which a contribution of impaired cholesterol metabolism to the disease has been proposed. For PD, several reports also indicated lysosomal system dysfunction associated with the pathogenesis of PD [143]. Of note, alteration in cholesterol metabolism has been found in PD patient-derived fibroblasts [144] and in the serum lipid profile of PD patients [145,146].…”

“…Honokiol (5,3 -diallyl-2,4 -dihydroxybiphenyl) [153,160] 12-(3-(adamantan-1-yl)ureido)dodecanoic acid (AUDA) [92,96] 1,3-bis (4-methoxybenzyl)urea (MMU) [159] N-(1-acetylpiperidin-4-yl)-N-(adamant-1-yl)urea (APAU) [170] (4-(5-phenyl-3-{3-[3-(4-trifluoromethyl-phenyl)-ureido]-propyl}-pyrazol-1-yl)-benzenesulfonamide) (PTUPB) [143] 1-((1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy) phenyl)) urea (TPPU) [109] Funding: This study was supported by the Ministerio de Economía, Industria y Competitividad (Agencia Estatal de Investigación, AEI) and Fondo Europeo de Desarrollo Regional (MINECO-FEDER) (Projects SAF2017-82771-R, SAF2016-33307, RTI2018-096429-B-100). C.G.-F., S.V., C.S., and M.P.…”

Impact of Sex and Age on the Mevalonate Pathway in the Brain: A Focus on Effects Induced by Maternal Exposure to Exogenous Compounds

“…Mutations in genes involved in the MVA pathway or cholesterol metabolism, cause neurologic and psychiatric diseases such as Smith–Lemli–Opitz syndrome (SLOS), Niemann-Pick type C disease (NPC), and desmosterolosis [ 26 ]. However, other brain diseases have been related to MVA/cholesterol metabolism such as Autism spectrum disorder (ASD) [ 2 ], Huntington’s disease (HD) [ 29 , 45 ], Alzheimer’s disease (AD) [ 27 , 46 , 47 , 48 ], and Parkinson disease (PD) [ 49 ]. Interestingly, most of them display sex-related differences either on the incidence or severity of symptoms, such as NPC [ 50 , 51 ], AD [ 52 , 53 , 54 ], ASD [ 55 , 56 , 57 ], PD and HD [ 58 ].…”