Amyloid-beta precursor protein

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Amyloid-beta precursor protein

The Amyloid-beta precursor protein (APP) is a transmembrane protein that plays a crucial role in the pathogenesis of Alzheimer's disease. It is encoded by the APP gene located on chromosome 21 in humans. APP is processed through two main pathways: the amyloidogenic pathway and the non-amyloidogenic pathway.

Structure

APP is a type I transmembrane protein that undergoes post-translational modifications, including glycosylation and phosphorylation. It consists of a large extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. The extracellular domain contains the amyloid-beta (Aβ) region, which is cleaved to form Aβ peptides.

Function

The exact function of APP is not fully understood, but it is believed to be involved in neuronal growth, synapse formation, and repair processes in the brain. APP is processed by enzymes called secretases, which cleave it at different sites to produce various fragments. The amyloidogenic pathway leads to the formation of Aβ peptides, which can aggregate and form plaques in the brain, a hallmark of Alzheimer's disease.

Role in Alzheimer's Disease

Mutations in the APP gene or abnormalities in its processing can lead to the accumulation of Aβ peptides, which are toxic to neurons and disrupt normal brain function. This accumulation is a key event in the development of Alzheimer's disease. The Aβ peptides can aggregate to form insoluble plaques, which contribute to neurodegeneration and cognitive decline.

Clinical Significance

Research on APP and its processing pathways is essential for understanding the mechanisms underlying Alzheimer's disease and developing potential therapeutic interventions. Targeting the processing of APP to reduce the production of Aβ peptides is a promising approach for treating Alzheimer's disease.

See also

• Alzheimer's disease
• Neurodegeneration
• Neuroscience