Presenilin

Presenilin is a class of transmembrane proteins that are essential components of the gamma-secretase complex. This complex plays a crucial role in the processing of various transmembrane proteins, most notably the amyloid precursor protein (APP). Mutations in presenilin genes, particularly PSEN1 and PSEN2, are the most common cause of early-onset familial Alzheimer's disease. These mutations lead to an altered cleavage of APP, resulting in the increased production of amyloid-beta peptides, which aggregate to form amyloid plaques in the brain, a hallmark of Alzheimer's pathology.

Beyond APP processing, presenilins are involved in a range of other cellular functions, including Notch signaling, which is critical for cell-to-cell communication and development. The exact mechanisms by which presenilin mutations contribute to neurodegeneration are still under active investigation, but research points to disruption of multiple signaling pathways and cellular processes. Presenilin proteins are found in various cellular compartments, including the endoplasmic reticulum and Golgi apparatus. Their role as the catalytic core of the gamma-secretase complex makes them a significant target for therapeutic strategies aimed at treating Alzheimer's disease, although developing selective inhibitors without causing off-target effects remains a challenge.