4.5 Article

Novel therapeutic strategies for Alzheimer's disease targeting brain cholesterol homeostasis

期刊

EUROPEAN JOURNAL OF NEUROSCIENCE
卷 53, 期 2, 页码 673-686

出版社

WILEY
DOI: 10.1111/ejn.14949

关键词

alternative strategies; Alzheimer's disease; cholesterol dysmetabolism; neurodegeneration; statins

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Alzheimer's disease is a progressive neurodegenerative disorder with A beta plaques and tauopathy as major concerns. Dysmetabolism of brain cholesterol is recognized as a crucial factor affecting the disease progression.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. A beta plaques and tauopathy are two major concerns associated with AD. Moreover, excessive A beta accumulation can lead to other nonspecific metabolic brain abnormalities. There are various genetic, environmental, and other risk factors associated with AD. Identification of risk factors and its mechanisms by which these factors impart role in AD pathology would be helpful for the prevention of AD progression. Altered cholesterol homeostasis could be considered as a risk factor for AD progression. Brain cholesterol dysmetabolism is recognized as one of the crucial attributes for AD that affect major hallmarks of AD including neurodegeneration. To fill the gap between altered cholesterol levels in the brain and AD, the researchers started focusing on statins as re-purposing drugs for AD treatment. The various other hypothesis has been suggested due to a lack of beneficial results of statins in clinical trials, such as reduced brain cholesterol could underlie poor cognition. Unfortunately, it is still unclear, whether an increase or decrease in brain cholesterol levels responsible for Alzheimer's disease or not. Presently, scientists believed that managing the level of cholesterol in the brain may help as an alternative treatment strategy for AD. In this review, we focused on the therapeutic strategies for AD by targeting brain cholesterol levels.

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