γ-Secretase, an intramembrane aspartyl protease that cleaves its substrates within their transmembrane domains, is composed of four subunits: presenilin (PS), nicastrin (Nct), Aph-1, and Pen-2. PS is the catalytic subunit of γ-secretase. Aberrant cleavage of two γ-secretase substrates, namely amyloid precursor protein (APP) and Notch, can lead to Alzheimer s disease (AD) and cancer, respectively. As a result of its role in these diseases, γ-secretase has emerged as an important drug target.
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