Presenilin mutations and their impact on neuronal differentiation in Alzheimer 's disease
Mercedes A.Hernández-Sapiéns1
Edwin E.Reza-Zaldívar1
Ana L.Márquez-Aguirre1
Ulises Gómez-Pinedo2
Jorge Matias-Guiu2
Ricardo R.Cevallos3
Juan C.Mateos-Díaz4
Víctor J.Sánchez-González5
Alejandro A.Canales-Aguirre1
1.Unidad de Evaluación Preclínica,Unidad de Biotecnología Médica y Farmacéutica,Centro de Investigación y Asistencia en Tecnología y Dise?o del Estado de Jalisco,Guadalajara,México2.Instituto de Neurociencias,IdISSC,Hospital Clínico San Carlos,Madrid,Espa?a3.Biochemistry and Molecular Genetics Department,University of Alabama,Birmingham,Alabama4.Unidad de Biotecnología Industrial,Centro de Investigación y Asistencia en Tecnología y Dise?o del Estado de Jalisco,Guadalajara,México5.Centro Universitario de los Altos,Universidad de Guadalajara,Guadalajara,México
摘要：The presenilin genes (PSEN1 and PSEN2) are mainly responsible for causing early-onset familial Alzheimer's disease, harboring ～300 causative mutations, and representing ～90％ of all mutations associated with a very aggressive disease form. Presenilin 1 is the catalytic core of the γ-secretase complex that conducts the intramembranous proteolytic excision of multiple transmembrane proteins like the amyloid precursor protein, Notch-1, N- and E-cadherin, LRP, Syndecan, Delta, Jagged, CD44, ErbB4, and Nectin1a. Presenilin 1 plays an essential role in neural progenitor maintenance, neurogenesis, neurite outgrowth, synaptic function, neuronal function, myelination, and plasticity. Therefore, an imbalance caused by mutations in presenilin 1/γ-secretase might cause aberrant signaling, synaptic dysfunction, memory impairment, and increased Aβ42/Aβ40 ratio, contributing to neurodegeneration during the initial stages of Alzheimer's disease pathogenesis. This review focuses on the neuronal differentiation dysregulation mediated by PSEN1 mutations in Alzheimer's disease. Furthermore, we emphasize the importance of Alzheimer's disease-induced pluripotent stem cells models in analyzing PSEN1 mutations implication over the early stages of the Alzheimer's disease pathogenesis throughout neuronal differentiation impairment.
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论文发表日期：2022-01-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：7( 31-37 )
英文信息