title: The presenilin 1 mutation (M146V) linked to familial Alzheimer's disease attenuates the neuronal differentiation of NTera 2 cells.
abstract: Mutations in presenilin 1 (PS1) gene are the major cause of early-onset familial Alzheimer's disease. The biological functions of PS1 remain elusive, although accumulating evidence suggests that PS1 may play an important role in development and differentiation. To learn about the significance of PS1 in the differentiation of neuronal cells, we established NTera 2 (NT2) cell lines stably expressing wild-type (wt) or M146V mutant human PS1, and compared the differentiation of both types of cell lines into postmitotic neurons upon retinoic acid (RA) treatment. After 25 days of RA treatment, a significant proportion of cells differentiated into neurons in NT2 cells expressing wt PS1 (27.7% of total cells), which was comparable to that in untransfected cells, whereas very few cells differentiated into neurons in NT2 cells expressing M146V mutant PS1 (2.6% of total cells). These results suggest that mutant PS1 attenuates the potentials of NT2 cells to differentiate into neurons.
authors.affiliation: Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tokuhiro
authors.forename: T
authors.initials: T
authors.lastname: Tomita
authors.forename: H
authors.initials: H
authors.lastname: Iwata
authors.forename: T
authors.initials: T
authors.lastname: Kosaka
authors.forename: T C
authors.initials: TC
authors.lastname: Saido
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.forename: T
authors.initials: T
authors.lastname: Iwatsubo
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D015870:Gene Expression; D008040:Genetic Linkage; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D009154:Mutation; D009474:Neurons / Q000502:physiology*; D053764:Presenilin-1; D011994:Recombinant Proteins / Q000096:biosynthesis; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011994:Recombinant Proteins; D014212:Tretinoin