New insight into the role of altered brain cholesterol metabolism in the pathogenesis of AD: a unifying cholesterol hypothesis and new therapeutic approach for AD DOI Creative Commons
Xiaobo Yang, Kai Yao, Mengqi Zhang

et al.

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111321 - 111321

Published: March 1, 2025

The dysregulation of cholesterol metabolism homeostasis has been universally suggested in the aeotiology Alzheimer's disease (AD). Initially, studies indicate that alteration serum level might contribute to AD. However, because blood-brain barrier impedes entry plasma cholesterol, brain cells are not directly influenced by cholesterol. Furthermore, mounting evidences suggest a link between and Interestingly, Amyloid-β proteins (Aβ) can markedly inhibit cellular biosynthesis lower content cultured cells. And Aβ overproduction/overload induces significant decrease familial AD (FAD) animals. Importantly, mutations or polymorphisms genes related transportation, such as ApoE4, ATP binding cassette (ABC) transporters, low-density lipoprotein receptor (LDLR) family Niemann-Pick C 1 2 (NPC1/2), obviously lead decreased transport, resulting loss, which could be tightly associated with pathological impairments. Additionally, accumulating data show there reduction and/or disorder trafficking variety sporadic (SAD) animals patients. Collectively, compelling FAD SAD share one common overlapping neurochemical mechanism: neuronal/cellular deficiency. Therefore, accumulated strongly support novel hypothesis deficiency contributes onset progression This review highlights pivotal role pathogenesis offers valuable insights for future development treatment.

Language: Английский

New insight into the role of altered brain cholesterol metabolism in the pathogenesis of AD: a unifying cholesterol hypothesis and new therapeutic approach for AD DOI Creative Commons
Xiaobo Yang, Kai Yao, Mengqi Zhang

et al.

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111321 - 111321

Published: March 1, 2025

The dysregulation of cholesterol metabolism homeostasis has been universally suggested in the aeotiology Alzheimer's disease (AD). Initially, studies indicate that alteration serum level might contribute to AD. However, because blood-brain barrier impedes entry plasma cholesterol, brain cells are not directly influenced by cholesterol. Furthermore, mounting evidences suggest a link between and Interestingly, Amyloid-β proteins (Aβ) can markedly inhibit cellular biosynthesis lower content cultured cells. And Aβ overproduction/overload induces significant decrease familial AD (FAD) animals. Importantly, mutations or polymorphisms genes related transportation, such as ApoE4, ATP binding cassette (ABC) transporters, low-density lipoprotein receptor (LDLR) family Niemann-Pick C 1 2 (NPC1/2), obviously lead decreased transport, resulting loss, which could be tightly associated with pathological impairments. Additionally, accumulating data show there reduction and/or disorder trafficking variety sporadic (SAD) animals patients. Collectively, compelling FAD SAD share one common overlapping neurochemical mechanism: neuronal/cellular deficiency. Therefore, accumulated strongly support novel hypothesis deficiency contributes onset progression This review highlights pivotal role pathogenesis offers valuable insights for future development treatment.

Language: Английский

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