Presenilin-2

Vertebrates have two presenilin genes, called PSEN1 (located on chromosome 14 in humans) that encodes presenilin 1 (PS-1) and PSEN2 (on chromosome 1 in humans) that codes for presenilin 2 (PS-2) . Both genes show conservation between species, with little difference between rat and human presenilins. The nematode worm C. elegans has two genes that resemble the presenilins and appear to be functionally similar, sel-12 and hop-1. Presenilins undergo cleavage in an alpha helical region of one of the cytoplasmic loops to produce a larger N-terminal and a smaller C-terminal fragment that together form part of the functional protein. Cleavage of presenilin 1 can be prevented by a mutation that causes the loss of exon 9, and results in loss of function. Presenilins play a key role in the modulation of intracellular Ca2+ involved in presynaptic neurotransmitter release and long-term potentiation induction.Dominant mutations in the genes that encode presenilin proteins are the most common cause of familial early-onset Alzheimer's disease.