HDL-like-Mediated Cell Cholesterol Trafficking in the Central Nervous System and Alzheimer's Disease Pathogenesis
Por:
Borras, C, Mercer, A, Sirisi, S, Alcolea, D, Escola-Gil, JC, Blanco-Vaca, F, Tondo, M
Publicada:
1 ago 2022
Resumen:
The main aim of this work is to review the mechanisms via which high-density lipoprotein (HDL)-mediated cholesterol trafficking through the central nervous system (CNS) occurs in the context of Alzheimer's disease (AD). Alzheimer's disease is characterized by the accumulation of extracellular amyloid beta (A beta) and abnormally hyperphosphorylated intracellular tau filaments in neurons. Cholesterol metabolism has been extensively implicated in the pathogenesis of AD through biological, epidemiological, and genetic studies, with the APOE gene being the most reproducible genetic risk factor for the development of AD. This manuscript explores how HDL-mediated cholesterol is transported in the CNS, with a special emphasis on its relationship to A beta peptide accumulation and apolipoprotein E (ApoE)-mediated cholesterol transport. Indeed, we reviewed all existing works exploring HDL-like-mediated cholesterol efflux and cholesterol uptake in the context of AD pathogenesis. Existing data seem to point in the direction of decreased cholesterol efflux and the impaired entry of cholesterol into neurons among patients with AD, which could be related to impaired A beta clearance and tau protein accumulation. However, most of the reviewed studies have been performed in cells that are not physiologically relevant for CNS pathology, representing a major flaw in this field. The ApoE4 genotype seems to be a disruptive element in HDL-like-mediated cholesterol transport through the brain. Overall, further investigations are needed to clarify the role of cholesterol trafficking in AD pathogenesis.
Filiaciones:
Borras, C:
Inst Invest Biomed Sant Pau IIB, Sant Quinti 77-79, Barcelona 08041, Spain
CIBERDEM, ISCIII, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Biochem & Mol Biol, Bellaterra 08193, Spain
Mercer, A:
Inst Invest Biomed Sant Pau IIB, Sant Quinti 77-79, Barcelona 08041, Spain
Sirisi, S:
Inst Invest Biomed Sant Pau IIB, Sant Quinti 77-79, Barcelona 08041, Spain
Hosp Santa Creu & Sant Pau, Dept Neurol, Sant Pau Memory Unit, Barcelona 08041, Spain
Alcolea, D:
Inst Invest Biomed Sant Pau IIB, Sant Quinti 77-79, Barcelona 08041, Spain
Hosp Santa Creu & Sant Pau, Dept Neurol, Sant Pau Memory Unit, Barcelona 08041, Spain
CIBERNED, ISCIII, Madrid 28029, Spain
Escola-Gil, JC:
Inst Invest Biomed Sant Pau IIB, Sant Quinti 77-79, Barcelona 08041, Spain
CIBERDEM, ISCIII, Madrid 28029, Spain
Blanco-Vaca, F:
Inst Invest Biomed Sant Pau IIB, Sant Quinti 77-79, Barcelona 08041, Spain
CIBERDEM, ISCIII, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Biochem & Mol Biol, Bellaterra 08193, Spain
Hosp Santa Creu & Sant Pau, Dept Biochem, Barcelona 08041, Spain
Tondo, M:
Inst Invest Biomed Sant Pau IIB, Sant Quinti 77-79, Barcelona 08041, Spain
CIBERDEM, ISCIII, Madrid 28029, Spain
Hosp Santa Creu & Sant Pau, Dept Biochem, Barcelona 08041, Spain
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