Alzheimer's Disease Pathology: Insig-1 Loss Connects Amyloid Beta to Abnormal Lipid Synthesis

Overview

Alzheimer's disease is a neurodegenerative disorder affecting millions, characterized by accumulation of amyloid beta oligomers causing neuronal dysfunction. The ubiquitin-proteasome system (UPS) degrades unnecessary and misfolded proteins. This study investigates whether amyloid beta-driven UPS dysregulation impairs lipid metabolism by observing insulin-induced gene-1 (Insig-1) and sterol regulatory element-binding portein-1 (SREBP1). Insig-1 prevents lipid synthesis by inhibiting SREBP1 activation. N2A neuronal cell model is treated with increasing amyloid beta concentrations, anti-ubiquitin immunoblot revealed progressive UPS dysregulation. Immunoprecipitation showed reduced Insig-1, releasing increased SREBP1 indicating abnormal lipid activation, shown via immunoblot. Supporting bioinformatics analysis demonstrates complete proteasome inhibition downregulates SREBP1, suggesting the degree of UPS dysregulation determines lipid dysregulation direction. Results reframe Alzheimer’s pathology with a feedback loop where amyloid beta-driven UPS dysregulation leads to abnormal lipid synthesis promoting amyloid beta production. The mechanistic link between amyloid beta-driven UPS deregulation and lipid synthesis is Insig-1, identifying Insig-1 as a potential target for Alzheimer’s.

Awards (2)

• Silver Medal
• Selected for CWSF 2026

Competition history

• CWSF 2026 Disease & Illness

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