Deletion of Dcf1 Reduces Amyloid-β Aggregation and Mitigates Memory Deficits
| Autor: | Yanhui Li, Fei-Yang Qian, Ruili Feng, Xin Diao, Jiao Wang, Weihao Li, Yangyang Sun, Yajiang Wang, Fang-Fang Ma, Linhua Gan, Tieqiao Wen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Amyloid β Conditioning Classical Hippocampus Mice Transgenic Nerve Tissue Proteins AMPA receptor Protein Aggregation Pathological Amyloid beta-Protein Precursor Mice 03 medical and health sciences 0302 clinical medicine Memory medicine Animals Humans Learning Receptors AMPA Senile plaques Pathological Aged 80 and over Mice Knockout Memory Disorders Amyloid beta-Peptides Neocortex biology business.industry General Neuroscience Membrane Proteins General Medicine Entorhinal cortex Psychiatry and Mental health Clinical Psychology Drosophila melanogaster 030104 developmental biology medicine.anatomical_structure biology.protein Geriatrics and Gerontology Antibody business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's Disease. 81:1181-1194 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-200619 |
| Popis: | Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease. One of the pathologies of AD is the accumulation of amyloid-β (Aβ) to form senile plaques, leading to a decline in cognitive ability and a lack of learning and memory. However, the cause leading to Aβ aggregation is not well understood. Dendritic cell factor 1 (Dcf1) shows a high expression in the entorhinal cortex neurons and neurofibrillary tangles in AD patients. Objective: Our goal is to investigate the effect of Dcf1 on Aβ aggregation and memory deficits in AD development. Methods: The mouse and Drosophila AD model were used to test the expression and aggregation of Aβ, senile plaque formation, and pathological changes in cognitive behavior during dcf1 knockout and expression. We finally explored possible drug target effects through intracerebroventricular delivery of Dcf1 antibodies. Results: Deletion of Dcf1 resulted in decreased Aβ42 level and deposition, and rescued AMPA Receptor (GluA2) levels in the hippocampus of APP-PS1-AD mice. In Aβ42 AD Drosophila, the expression of Dcf1 in Aβ42 AD flies aggravated the formation and accumulation of senile plaques, significantly reduced its climbing ability and learning-memory. Data analysis from all 20 donors with and without AD patients aged between 80 and 90 indicated a high-level expression of Dcf1 in the temporal neocortex. Dcf1 contributed to Aβ aggregation by UV spectroscopy assay. Intracerebroventricular delivery of Dcf1 antibodies in the hippocampus reduced the area of senile plaques and reversed learning and memory deficits in APP-PS1-AD mice. Conclusion: Dcf1 causes Aβ-plaque accumulation, inhibiting dcf1 expression could potentially offer therapeutic avenues. |
| Databáze: | OpenAIRE |
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