Relationship between Brain Metabolic Disorders and Cognitive Impairment: LDL Receptor Defect |
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| Authors: | Dong-Yong Hong Dong-Hun Lee Ji-Young Lee Eun-Chae Lee Sang-Won Park Man-Ryul Lee Jae-Sang Oh |
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| Affiliation: | 1.Department of Neurosurgery, College of Medicine, Soonchunhyang University, Cheonan Hospital, Cheonan 31151, Korea; (D.-Y.H.); (D.-H.L.); (J.-Y.L.); (E.-C.L.); (S.-W.P.);2.Soonchunhyang Institute of Medi-Bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, Korea |
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| Abstract: | The low-density-lipoprotein receptor (LDLr) 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 LDLr. LDLr co-localizes with the insulin receptor and complements the internalization of LDL. In LDLr 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 (ApoE) regulates the levels of amyloid beta (Aβ) in the brain, and hypoxia is induced by apoptosis induced by the LDLr defect. This review summarizes the association between neurodegenerative brain disease and typical cognitive deficits. |
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| Keywords: | cholesterol metabolism, LDLr, insulin receptor, SREBP, blood– brain-barrier (BBB) breakdown, neuroinflammation, ER stress, mitochondria, apoptosis, lectin-like oxidized LDL receptor-1 (LOX-1) |
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