CYP46A1-Mediated Cholesterol Reduction Prevents eIF2α-Driven Translation Stalling in Neurodegeneration

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This hypothesis proposes that CYP46A1 overexpression gene therapy prevents neurodegeneration by disrupting the pathological link between cholesterol dysregulation and eIF2α phosphorylation-mediated translation stalling. Elevated brain cholesterol in neurodegenerative diseases creates lipid raft instability that triggers endoplasmic reticulum stress, activating PERK kinase and leading to sustained