title: Pro-apoptotic effects of tau mutations in chromosome 17 frontotemporal dementia and parkinsonism.
abstract: It was recently discovered that mutations of tau cause hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Here we report that cultured SH-SY5Y human neuroblastoma cells transfected with mutated tau genes are more vulnerable to apoptotic stimulus. Two kinds of mutations of tau causing FTDP-17 were examined in the present study: one was in exon 10 (N279K) and the other was in exon 12 (V337M). SH-SY5Y cells transfected with either mutated tau were more vulnerable to serum withdrawal, whereas cells transfected with the wild-type tau or vector alone showed no significant change in apoptotic vulnerability. The increase in the intracellular calcium concentration by the serum withdrawal was significantly greater in the SH-SY5Y cells transfected with mutated tau genes than in cells transfected with the wild-type tau or vector alone. These results suggest that mutations of tau might cause FTDP-17 by these pro-apoptotic functions by disrupting the intracellular calcium homeostasis.
authors.affiliation: Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
authors.forename: K
authors.initials: K
authors.lastname: Furukawa
authors.forename: I
authors.initials: I
authors.lastname: D'Souza
authors.forename: C H
authors.initials: CH
authors.lastname: Crudder
authors.forename: H
authors.initials: H
authors.lastname: Onodera
authors.forename: Y
authors.initials: Y
authors.lastname: Itoyama
authors.forename: P
authors.initials: P
authors.lastname: Poorkaj
authors.forename: T D
authors.initials: TD
authors.lastname: Bird
authors.forename: G D
authors.initials: GD
authors.lastname: Schellenberg
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D002460:Cell Line; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D003704:Dementia / Q000235:genetics* / Q000473:pathology; D005091:Exons / Q000235:genetics; D005625:Frontal Lobe / Q000473:pathology / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D009154:Mutation / Q000235:genetics* / Q000502:physiology; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013702:Temporal Lobe / Q000473:pathology / Q000502:physiology*; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000235:genetics*
chemical_list: D016875:tau Proteins; D004247:DNA