Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts

Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts

Formation of senile plaques containing the beta-amyloid peptide (A beta) derived from the amyloid precursor protein (APP) is an invariant feature of Alzheimer's disease (AD). APP is cleaved either by beta-secretase or by alpha-secretase to initiate amyloidogenic (release of A beta) or nonamyloidogenic processing of APP, respectively. A key to understanding AD is to unravel how access of these e...

Palmitoylation of amyloid precursor protein regulates amyloidogenic processing in lipid rafts.

Brains of patients affected by Alzheimer's disease (AD) contain large deposits of aggregated amyloid β-protein (Aβ). Only a small fraction of the amyloid precursor protein (APP) gives rise to Aβ. Here, we report that ∼10% of APP undergoes a post-translational lipid modification called palmitoylation. We identified the palmitoylation sites in APP at Cys¹⁸⁶ and Cys¹⁸⁷. Surprisingly, point mutatio...

Mechanism of Alzheimer Amyloid β-Protein Precursor Localization to Membrane Lipid Rafts

AMPA Receptor Activation Promotes Non-Amyloidogenic Amyloid Precursor Protein Processing and Suppresses Neuronal Amyloid-β Production

Soluble oligomeric amyloid β peptide (Aβ) generated from processing of the amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimer's Disease (AD) and through actions at glutamatergic synapses affects excitability and plasticity. The physiological control of APP processing is not fully understood but stimulation of synaptic NMDA receptors (NMDAR) can suppress Aβ lev...

Amyloidogenic Processing of APP in Lipid Rafts

Increased generation of amyloid peptide (A ) derived from amyloid precursor protein (APP) is the primary pathological characteristic of Alzheimer’s disease (AD). However, the sub cellular compartment in which APP undergoes cleavage by secretases to generate A is not precisely known. Compelling evidences suggest that amyloidogenic processing of APP occurs in lipid rafts. An indirect support for ...