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C/EBPβ/AEP Signaling Drives Alzheimer's Disease Pathogenesis
Jing Xiong1, Zhentao Zhang1, Keqiang Ye2
1Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Neuroscience Bulletin
|February 3, 2023
Summary
Female susceptibility to Alzheimer's disease (AD) is linked to menopause. Follicle-stimulating hormone (FSH) activates the C/EBPβ/AEP pathway, worsening AD pathology and cognitive decline in women.
Area of Science:
- Neuroscience
- Endocrinology
- Pathology
Background:
- Alzheimer's disease (AD) is the leading cause of dementia, disproportionately affecting women.
- Hormonal shifts during menopause are implicated in the increased risk of AD in females.
- The precise mechanisms underlying female susceptibility to AD remain largely unknown.
Purpose of the Study:
- To review the role of the follicle-stimulating hormone (FSH)-activated CCAAT-enhancer-binding protein (C/EBPβ)/asparagine endopeptidase (AEP) pathway in AD pathogenesis.
- To elucidate the mechanisms by which FSH contributes to AD in postmenopausal women.
- To identify the FSH-C/EBPβ/AEP pathway as a potential therapeutic target for AD.
Main Methods:
- Literature review focusing on recent findings regarding the C/EBPβ/AEP pathway in AD.
- Analysis of the molecular mechanisms of FSH action in promoting AD pathology.
- Examination of the cleavage of key AD proteins like APP and Tau by AEP.
Main Results:
- FSH promotes AD pathology and cognitive dysfunction by activating the C/EBPβ/AEP pathway.
- The C/EBPβ/AEP pathway cleaves critical AD-related proteins, including Amyloid Precursor Protein (APP) and Tau.
- This pathway explains how FSH increases AD susceptibility in postmenopausal females.
Conclusions:
- The FSH-C/EBPβ/AEP pathway plays a critical role in AD pathogenesis.
- Understanding this pathway offers insights into why women are more susceptible to AD.
- Targeting the FSH-C/EBPβ/AEP pathway presents a novel therapeutic strategy for Alzheimer's disease treatment.