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 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

作者机构：Unidad de Evaluación PreclínicaUnidad de Biotecnología Médica y FarmacéuticaCentro de Investigación y Asistencia en Tecnología y Diseño del Estado de JaliscoGuadalajaraMéxico Instituto de NeurocienciasIdISSCHospital Clínico San CarlosMadridEspaña Biochemistry and Molecular Genetics DepartmentUniversity of AlabamaBirminghamAlabama Unidad de Biotecnología IndustrialCentro de Investigación y Asistencia en Tecnología y Diseño del Estado de JaliscoGuadalajaraMéxico Centro Universitario de los AltosUniversidad de GuadalajaraGuadalajaraMéxico 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2022年第17卷第1期

页      面：31-37页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100203[医学-老年医学] 10[医学] 

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

主　　题：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 

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.