PSEN1 encodes presenilin-1, a subunit of γ-secretase, the aspartyl protease responsible for Aβ generation. More than 300 mutations in PSEN1 have been reported and mutations in PSEN1 are the most common cause of early onset Alzheimer's disease. PDF (1.24 MB)

View PSEN1 on AlzGene. Mutations. Mutations in PSEN1 are a common cause of familial early onset Alzheimer's disease. Research Models. View mouse models with modifications in PSEN1 in the Research Models database. Therapeutics. View therapeutics that target γ-secretase in the Therapeutics database.

2002年7月11日 · APP, PSEN1, and PSEN2 Variants in Alzheimer's Disease: Systematic Re-evaluation According to ACMG Guidelines. Front Aging Neurosci. 2021;13:695808. Epub 2021 Jun 18 PubMed. Frederiksen HR, Holst B, Mau-Holzmann UA, Freude K, Schmid B. Generation of two isogenic iPSC lines with either a heterozygous or a homozygous E280A mutation in the …

2024年7月8日 · The PSEN1 ΔE9 mutations include three deletion mutations, one insertion mutation, and three splice-site mutations within intron 8. Despite their heterogeneity, they all result in the absence of exon 9 from transcripts and the production of presenilin protein lacking a region of about 30 amino acids.

2024年2月14日 · Additional cellular functions have been reported to be impaired in cells expressing this mutant. For example, compared with cells expressing wild-type PSEN1, neurite outgrowth was inhibited in N2a cells expressing P117L, as was neurofilament assembly (Dowjat et al., 1999; Dowjat et al., 2001).

2022年3月4日 · The H163R mutation was first described in 1995 in conjunction with the cloning of the PSEN1 gene. It was detected in two families, one American (Pedigree 603) and one French-Canadian (Tor42). The mutation was shown to segregate with early onset familial Alzheimer’s disease in both families, the latter with onset around 45 years of age ...

2022年8月11日 · These findings were confirmed and extended in a study of human embryonic kidney cells lacking endogenous PSEN1/PSEN2 and expressing M146V showing that the Aβ37/Aβ42 ratio, reported to outperform the Aβ42/Aβ40 ratio as an indicator of AD pathogenicity, was decreased relative to cells expressing wildtype PSEN1 (Liu et al., 2022, Apr 2022 news).

2018年1月10日 · A cryo-electron microscopy study of the atomic structure of γ-secretase bound to an APP fragment indicated that, in wild-type PSEN1, this residue is apposed to the APP transmembrane helix, with its side-chain reaching towards the interior of the substrate-binding pore (Zhou et al., 2019; Jan 2019 news).

PSEN1. PSEN1 encodes presenilin-1, a subunit of γ-secretase, the aspartyl protease responsible for Aβ generation. More than 300 mutations in PSEN1 have been reported and mutations in PSEN1 are the most common cause of early onset Alzheimer's disease.

2018年6月21日 · Mutation profile of APP, PSEN1, and PSEN2 in Chinese familial Alzheimer's disease. Neurobiol Aging. 2019 May;77:154-157. Epub 2019 Jan 31 PubMed. Lin YS, Cheng CY, Liao YC, Hong CJ, Fuh JL. Mutational analysis in familial Alzheimer's disease of Han Chinese in Taiwan with a predominant mutation PSEN1 p.Met146Ile. Sci Rep. 2020 Nov 13;10(1):19769 ...