TY - JOUR
T1 - Pro-apoptotic effects of tau mutations in chromosome 17 frontotemporal dementia and parkinsonism
AU - Furukawa, Katsutoshi
AU - D'Souza, Ian
AU - Crudder, Christopher H.
AU - Onodera, Hiroshi
AU - Itoyama, Yasuto
AU - Poorkaj, Parvoneh
AU - Bird, Thomas D.
AU - Schellenberg, Gerard D.
PY - 2000/1/17
Y1 - 2000/1/17
N2 - 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.
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.
KW - Apoptosis
KW - Calcium
KW - Frontotemporal dementia and parkinsonism
KW - Mutation
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=0034677185&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034677185&partnerID=8YFLogxK
U2 - 10.1097/00001756-200001170-00011
DO - 10.1097/00001756-200001170-00011
M3 - Article
C2 - 10683829
AN - SCOPUS:0034677185
VL - 11
SP - 57
EP - 60
JO - NeuroReport
JF - NeuroReport
SN - 0959-4965
IS - 1
ER -