Abstract：
:Tau, a microtubule binding protein, is not only a major component of neurofibrillary tangles in Alzheimer's disease, but also a causative gene for hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We show here that an FTDP-17 tau mutation (V337M) in SH-SY5Y cells reduces microtubule polymerization, increases voltage-dependent calcium current (ICa) density, and decreases ICa rundown. The reduced rundown of ICa by V337M was significantly inhibited by nifedipine (L-type Ca channel blocker), whereas omega-conotoxin GVIA (N-type Ca channel blocker) showed smaller effects, indicating that tau mutations affect L-type calcium channel activity. The depolarization-induced increase in intracellular calcium was also significantly augmented by the V337M tau mutation. Treatment with a microtubule polymerizing agent (taxol), an adenylyl cyclase inhibitor, or a protein kinase A (PKA) inhibitor, counteracted the effects of mutant tau on ICa. Taxol also attenuated the Ca2+ response to depolarization in cells expressing mutant tau. Apoptosis in SH-SY5Y cells induced by serum deprivation was exacerbated by the V337M mutation, and nifedipine, taxol, and a PKA inhibitor significantly protected cells against apoptosis. Our results indicate that a tau mutation which decreases its microtubule-binding ability augments calcium influx by depolymerizing microtubules and activating adenylyl cyclase and PKA.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Furukawa K,Wang Y,Yao PJ,Fu W,Mattson MP,Itoyama Y,Onodera H,D'Souza I,Poorkaj PH,Bird TD,Schellenberg GDdoi
10.1046/j.1471-4159.2003.02020.xkeywords:
subject
Has Abstractpub_date
2003-10-01 00:00:00pages
427-36issue
2eissn
0022-3042issn
1471-4159pii
2020journal_volume
87pub_type
杂志文章abstract：:2'-Deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase (ADA), is increasingly used as a tool to investigate adenosine metabolism and neuromodulation. To advance further the usefulness of DCF for studies of purines in the CNS, we determined the inhibitory potency of this compound against ADA and adenylate ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb01945.x
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doi：10.1111/j.1471-4159.1987.tb01028.x
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doi：10.1111/j.1471-4159.1985.tb12877.x
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pub_type： 杂志文章
doi：10.1111/j.1471-4159.2008.05614.x
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journal_title：Journal of neurochemistry
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更新日期：1991-11-01 00:00:00
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pub_type： 杂志文章
doi：10.1111/j.1471-4159.1988.tb01118.x
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pub_type： 杂志文章
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更新日期：1984-04-01 00:00:00
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pub_type： 杂志文章
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更新日期：1992-08-01 00:00:00
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更新日期：2016-12-01 00:00:00
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更新日期：2008-05-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb12525.x
更新日期：1981-09-01 00:00:00
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pub_type： 杂志文章
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更新日期：1985-03-01 00:00:00
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pub_type： 杂志文章
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更新日期：1996-06-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.740501.x
更新日期：2000-02-01 00:00:00
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更新日期：2004-03-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
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更新日期：2011-05-01 00:00:00
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doi：10.1046/j.1471-4159.1994.62041635.x
更新日期：1994-04-01 00:00:00
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pub_type： 杂志文章
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更新日期：2008-11-01 00:00:00
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journal_title：Journal of neurochemistry
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更新日期：2007-02-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb11840.x
更新日期：1983-07-01 00:00:00
abstract：:The metabolism of L-tryptophan to the neuroactive kynurenine pathway metabolites, L-kynurenine, kynurenate and quinolinate, and the effects of two inhibitors of quinolinate synthesis (6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate) were investigated by mass spectrometric assays in cultured cells and in vivo. Ce...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
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更新日期：1995-11-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
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更新日期：1987-12-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
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更新日期：1994-12-01 00:00:00
abstract：:Mutations within the amyloid-beta (Abeta) domain of the amyloid precursor protein (APP) typically generate hemorrhagic strokes and vascular amyloid angiopathy. In contrast, the Arctic mutation (APP E693G) results in Alzheimer's disease. Little is known about the pathologic mechanisms that result from the Arctic mutati...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
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更新日期：2007-05-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb11801.x
更新日期：1989-09-01 00:00:00
