Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s disease  

作　　者：Mercedes A.Hernández-Sapiéns Edwin E.Reza-Zaldívar Ana L.Márquez-Aguirre Ulises Gómez-Pinedo Jorge Matias-Guiu Ricardo R.Cevallos Juan C.Mateos-Díaz Víctor J.Sánchez-González Alejandro A.Canales-Aguirre 

机构地区：[1]Unidad de Evaluación Preclínica,Unidad de Biotecnología Médica y Farmacéutica,Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco,Guadalajara,México [2]Instituto de Neurociencias,IdISSC,Hospital Clínico San Carlos,Madrid,España [3]Biochemistry and Molecular Genetics Department,University of Alabama,Birmingham,Alabama [4]Unidad de Biotecnología Industrial,Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco,Guadalajara,México [5]Centro Universitario de los Altos,Universidad de Guadalajara,Guadalajara,México

出　　处：《Neural Regeneration Research》2022年第1期31-37,共7页中国神经再生研究（英文版）

基　　金：supported by the Consejo Nacional de Ciencia y Tecnología Scholarship 711893(to MAH)and 711874(to EER)。

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 theγ-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.

关 键 词：familial Alzheimer’s disease familial Alzheimer’s disease-induced pluripotent stem cells models induced pluripotent stem cells neurogenesis neuronal differentiation Notch presenilin 1 PSEN1 mutations γ-secretase complex 

分 类 号：R749.16[医药卫生—神经病学与精神病学]