Molecular Dynamics of Apolipoprotein Genotypes APOE4 and SNARE Family Proteins and Their Impact on Alzheimer's Disease.

ABSTRACT: Alzheimer's disease is a chronic neurodegenerative disorder characterized by progressive memory loss and a significant impact on quality of life. The APOE ε4 allele is a major genetic contributor to AD pathogenesis, with synaptic dysfunction being a central hallmark in its pathophysiology. While the role of APOE4 in reducing SNARE protein levels has been established, the underlying molecular mechanisms of this interaction remain obscure. Our research employs molecular dynamics simulations to analyze interactions between APOE4 and APOE3 isoforms and the synaptic proteins VAMP2, SNAP25, and SYNTAXIN1, which play crucial roles in the presynaptic membrane. Our findings reveal that APOE4 significantly destabilizes the SNARE complex, suppresses its structural dynamics, and reduces hydrogen bondi

SUBMITTER: Wang Y 

PROVIDER: S-EPMC11855958 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature