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01.12.2020 | Review Article

Exploring the Role of PSEN Mutations in the Pathogenesis of Alzheimer’s Disease

verfasst von: Md. Tanvir Kabir, Md. Sahab Uddin, Jinnat Ruksana Setu, Ghulam Md Ashraf, May N. Bin-Jumah, Mohamed M. Abdel-Daim

Erschienen in: Neurotoxicity Research | Ausgabe 4/2020

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Abstract

Alzheimer’s disease (AD) is the most common cause of dementia. Mutations of presenilin (PSEN) genes that encode presenilin proteins have been found as the vital causal factors for early-onset familial AD (FAD). AD pathological features such as memory loss, synaptic dysfunction, and formation of plaques have been successfully mimicked in the transgenic mouse models that coexpress FAD-related presenilin and amyloid precursor protein (APP) variants. γ-Secretase (GS) is an enzyme that plays roles in catalyzing intramembranous APP proteolysis to release pathogenic amyloid beta (Aβ). It has been found that presenilins can play a role as the GS’s catalytic subunit. FAD-related mutations in presenilins can modify the site of GS cleavage in a way that can elevate the production of longer and highly fibrillogenic Aβ. Presenilins can interact with β-catenin to generate presenilin complexes. Aforesaid interactions have also been studied to observe the mutational and physiological activities in the catenin signal transduction pathway. Along with APP, GS can catalyze intramembrane proteolysis of various substrates that play a vital role in synaptic function. PSEN mutations can cause FAD with autosomal dominant inheritance and early onset of the disease. In this article, we have reviewed the current progress in the analysis of PSENs and the correlation of PSEN mutations and AD pathogenesis.

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Titel: Exploring the Role of PSEN Mutations in the Pathogenesis of Alzheimer’s Disease
verfasst von: Md. Tanvir Kabir
Md. Sahab Uddin
Jinnat Ruksana Setu
Ghulam Md Ashraf
May N. Bin-Jumah
Mohamed M. Abdel-Daim
Publikationsdatum: 01.12.2020
Verlag: Springer US
Erschienen in: Neurotoxicity Research / Ausgabe 4/2020
Print ISSN: 1029-8428
Elektronische ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-020-00232-x

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Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

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