PMID- 10683829 OWN - NLM STAT- MEDLINE DCOM- 20000316 LR - 20190718 IS - 0959-4965 (Print) IS - 0959-4965 (Linking) VI - 11 IP - 1 DP - 2000 Jan 17 TI - Pro-apoptotic effects of tau mutations in chromosome 17 frontotemporal dementia and parkinsonism. PG - 57-60 AB - 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. FAU - Furukawa, K AU - Furukawa K AD - Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA. FAU - D'Souza, I AU - D'Souza I FAU - Crudder, C H AU - Crudder CH FAU - Onodera, H AU - Onodera H FAU - Itoyama, Y AU - Itoyama Y FAU - Poorkaj, P AU - Poorkaj P FAU - Bird, T D AU - Bird TD FAU - Schellenberg, G D AU - Schellenberg GD LA - eng PT - Journal Article PL - England TA - Neuroreport JT - Neuroreport JID - 9100935 RN - 0 (tau Proteins) RN - 9007-49-2 (DNA) SB - IM MH - Apoptosis/*genetics MH - Blotting, Western MH - Cell Line MH - Chromosomes, Human, Pair 17/*genetics MH - DNA/genetics MH - Dementia/*genetics/pathology MH - Exons/genetics MH - Frontal Lobe/pathology/*physiology MH - Homeostasis MH - Humans MH - Mutation/*genetics/physiology MH - Parkinson Disease/*genetics/pathology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Temporal Lobe/pathology/*physiology MH - Transfection/genetics MH - Tumor Cells, Cultured MH - tau Proteins/*genetics EDAT- 2000/02/23 09:00 MHDA- 2000/03/18 09:00 CRDT- 2000/02/23 09:00 PHST- 2000/02/23 09:00 [pubmed] PHST- 2000/03/18 09:00 [medline] PHST- 2000/02/23 09:00 [entrez] AID - 10.1097/00001756-200001170-00011 [doi] PST - ppublish SO - Neuroreport. 2000 Jan 17;11(1):57-60. doi: 10.1097/00001756-200001170-00011.