Type: dissertation
Abstract: Alzheimer's disease (AD) is characterized by the formation of extracellular amyloid plaques containing the amyloid -protein (A) within the parenchyma of the brain.A42, which is 42 amino acids in length, is considered to be the key pathogenic factor in AD.Iron deposition is found abundantly in the amyloid plaques of AD patients; however, whether iron intake exacerbates amyloid deposition in vivo is unknown.Here, we treated AD model mice with iron-containing water and found that A42 deposition in the brain was significantly inhibited, along with a decrease in iron deposition.Iron treatment did not change the overall levels of iron in the brain or serum.Interestingly, A40 generation was significantly increased by iron treatment in amyloid precursor protein (APP)-overexpressing fibroblasts, whereas A42 generation did not change, which led to a decreased A42/A40 ratio.We found that ferritin bound to presenilin 1 and that iron treatment increased this binding.Because A40 can inhibit A42 aggregation in vitro, and A40 inhibits amyloid formation in vivo, our results suggest that iron can selectively enhance A40 generation by modulating γ-secretase and inhibit amyloid deposition by reducing the A42/A40 ratio.Thus, iron may be used as a novel treatment for reducing the A42/A40 ratio and A42 deposition in AD.
Author: 沈, 雪峰
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7208592056