Presenilin 2

Presenilin 2 (PSEN2) is a protein that in humans is encoded by the PSEN2 gene. Presenilin 2 is a component of the gamma-secretase complex, which is involved in the intramembrane proteolysis of several type I transmembrane proteins, including the amyloid precursor protein (APP). This process is crucial in the pathogenesis of Alzheimer's disease.

Structure

Presenilin 2 is a multi-pass transmembrane protein that is predominantly located in the endoplasmic reticulum and Golgi apparatus. It shares a high degree of homology with Presenilin 1, another component of the gamma-secretase complex. The protein consists of several transmembrane domains and a large cytoplasmic loop.

Function

Presenilin 2 is an integral part of the gamma-secretase complex, which also includes nicastrin, APH-1, and PEN-2. This complex is responsible for the cleavage of APP, leading to the production of amyloid-beta peptides. These peptides can aggregate to form amyloid plaques, a hallmark of Alzheimer's disease pathology.

In addition to its role in APP processing, presenilin 2 is involved in the cleavage of other substrates, such as Notch, which is important for cell differentiation processes.

Clinical Significance

Mutations in the PSEN2 gene have been linked to familial Alzheimer's disease (FAD), a hereditary form of the disease. Although less common than mutations in PSEN1, PSEN2 mutations can lead to early-onset Alzheimer's disease. The most well-known mutation is the N141I mutation, which has been identified in several families with a history of Alzheimer's disease.

Research

Ongoing research is focused on understanding the precise mechanisms by which presenilin 2 mutations contribute to Alzheimer's disease. This includes studies on the structure and function of the gamma-secretase complex, as well as the development of potential therapeutic agents that target this pathway.

Also see

• Presenilin 1
• Gamma-secretase
• Amyloid precursor protein
• Alzheimer's disease
• Notch signaling pathway