Amyloid β regulates the expression and function of AIP1

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Alzheimer's disease (AD) involves complex cellular mechanisms.
• Apoptosis signal-regulating kinase 1-interacting protein-1 (AIP1) is a Ras GTPase-activating protein family member linked to apoptosis.
• The role of AIP1 in AD pathogenesis remains unexplored.

Purpose of the Study:

• To investigate the role and mechanism of AIP1 in Alzheimer's disease (AD).
• To determine the effect of amyloid-beta (Aβ) on AIP1 expression and activity in brain cells.

Main Methods:

• Western blotting and co-immunoprecipitation assays were used to analyze protein interactions and levels.
• Aβ1-42 treatment was applied to Tg2576 mouse brains and cerebral microvascular endothelial cells (CECs).
• RNA interference (siRNA) was employed to silence AIP1 expression.

Main Results:

• AIP1 levels were elevated in AD mouse brains and Aβ1-42 treated CECs.
• Aβ1-42 induced AIP1 interaction with ASK1, causing dissociation from 14-3-3 and ASK1 activation (Ser-967 dephosphorylation).
• AIP1 silencing prevented Aβ-induced ASK1 activation, JNK/p53 signaling, and CEC apoptosis.

Conclusions:

• AIP1 mediates Aβ-induced ASK1 activation by disrupting the ASK1-14-3-3 complex.
• AIP1 plays a critical role in Aβ-induced apoptosis in cerebral microvascular endothelial cells.
• AIP1 represents a potential therapeutic target for mitigating apoptosis in Alzheimer's disease.