| Modification Notes |
Presenilins are components of a protease complex that functions to cleave Notch receptors and the Amyloid precursor protein implicated in Alzheimer’s disease. Mutations in Presenilin 1 and Presenilin 2 are the most common cause of familial early-onset Alzheimer’s disease. A mutation in the Sel-12 presenilin protein is associated with a highly penetrant egg-laying defect caused by a reduction in Notch signaling. The transgenic expression of HOP-1 can rescue a SEL-12 mutant from the egg-laying defect. SPR-5 (suppressor of presenilin defect family member 5) is a 770 amino acid protein that, when mutated, efficiently suppresses the egg-laying defect of the SEL-12 mutant by releasing the repression of HOP-1 expression during developmental stages. SPR-5 is similar to the mammalian PAO protein and is believed to associate with SPR-1, a C. elegans homolog of CoREST-like co-repressor complex that functions in transcriptional repression. |
