Gamma secretase

Gamma secretase is an intramembrane-cleaving protease, a type of enzyme that plays a crucial role in various cellular processes, including the pathogenesis of Alzheimer's disease. It is a multi-subunit complex composed of four core proteins: Presenilin, Nicastrin, Aph-1, and Pen-2.

Function

Gamma secretase is responsible for the proteolytic cleavage of several type I integral membrane proteins, including the amyloid precursor protein (APP). The cleavage of APP by gamma secretase produces amyloid beta peptides, which aggregate to form the amyloid plaques found in the brains of Alzheimer's disease patients.

Structure

The gamma secretase complex is composed of four core proteins: Presenilin, which is the catalytic subunit of the complex; Nicastrin, which is involved in substrate recognition; Aph-1, which is required for complex assembly; and Pen-2, which is necessary for endoproteolysis of presenilin and activation of the complex.

Role in Disease

Mutations in the genes encoding the gamma secretase complex proteins, particularly presenilin, have been linked to early-onset familial Alzheimer's disease. Inhibition of gamma secretase activity is therefore a potential therapeutic strategy for Alzheimer's disease. However, because gamma secretase cleaves many different substrates, its inhibition could also have adverse side effects.

See Also

• Alzheimer's disease
• Amyloid precursor protein
• Presenilin
• Nicastrin
• Aph-1
• Pen-2