Relationship between Brain Metabolic Disorders and Cognitive Impairment: LDL Receptor Defect

The low-density-lipoprotein receptor (<i>LDLr</i>) removes low-density lipoprotein (LDL), an endovascular transporter that carries cholesterol from the bloodstream to peripheral tissues. The maintenance of cholesterol content in the brain, which is important to protect brain function, is...

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Bibliographic Details
Main Authors: Dong-Yong Hong, Dong-Hun Lee, Ji-Young Lee, Eun-Chae Lee, Sang-Won Park, Man-Ryul Lee, Jae-Sang Oh
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/15/8384
Description
Summary:The low-density-lipoprotein receptor (<i>LDLr</i>) removes low-density lipoprotein (LDL), an endovascular transporter that carries cholesterol from the bloodstream to peripheral tissues. The maintenance of cholesterol content in the brain, which is important to protect brain function, is affected by <i>LDLr</i>. <i>LDLr</i> co-localizes with the insulin receptor and complements the internalization of LDL. In <i>LDLr</i> deficiency, LDL blood levels and insulin resistance increase, leading to abnormal cholesterol control and cognitive deficits in atherosclerosis. Defects in brain cholesterol metabolism lead to neuroinflammation and blood–brain-barrier (BBB) degradation. Moreover, interactions between endoplasmic reticulum stress (ER stress) and mitochondria are induced by ox-LDL accumulation, apolipoprotein E (<i>ApoE</i>) regulates the levels of amyloid beta (Aβ) in the brain, and hypoxia is induced by apoptosis induced by the <i>LDLr</i> defect. This review summarizes the association between neurodegenerative brain disease and typical cognitive deficits.
ISSN:1661-6596
1422-0067