Reference Report

Reference
Citation	Khurana, V., Lu, Y., Steinhilb, M.L., Oldham, S., Shulman, J.M., Feany, M.B. (2006). TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model. Curr. Biol. 16(3): 230--241. (Export to RIS)
FlyBase ID	FBrf0190026
Publication Type	Research paper
PubMed ID	16461276
PubMed Abstract	Previous studies have demonstrated reexpression of cell-cycle markers within postmitotic neurons in neurodegenerative tauopathies, including Alzheimer's disease (AD). However, the critical questions of whether cell-cycle activation is causal or epiphenomenal to tau-induced neurodegeneration and which signaling pathways mediate cell-cycle activation in tauopathy remain unresolved.Cell-cycle activation accompanies wild-type and mutant tau-induced neurodegeneration in Drosophila, and genetically interfering with cell-cycle progression substantially reduces neurodegeneration. Our data support a role for cell-cycle activation downstream of tau phosphorylation, directly preceding apoptosis. We accordingly show that ectopic cell-cycle activation leads to apoptosis of postmitotic neurons in vivo. As in AD, TOR (target of rapamycin kinase) activity is increased in our model and is required for neurodegeneration. TOR activation enhances tau-induced neurodegeneration in a cell cycle-dependent manner and, when ectopically activated, drives cell-cycle activation and apoptosis in postmitotic neurons.TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model, identifying TOR and the cell cycle as potential therapeutic targets in tauopathies and AD.
DOI
Related Publication(s)
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
Language of Publication	English
Additional Languages of Abstract
Also Published As
Parent Publication
Publication Type	Journal
Abbreviation	Curr. Biol.
Title	Current Biology
Publication Year	1991-
ISBN/ISSN	0960-9822
Data from Reference
Aberrations (2)
	Df(3R)e-BS2 Df(3R)e-N19
Alleles (42)
	cdc2^{E51Q.Scer\UAS} cdc2^Scer\UAS.cWa cdc2c^{Scer\UAS.T:Hsap\MYC} Cdk4³ Cdk4^Scer\UAS.cMa CycA^C8LR1 CycA^Scer\UAS.cWa CycB3^L6540 CycB^Scer\UAS.cWa CycD^Scer\UAS.cMa CycE^Scer\UAS.cUa dap^{Scer\UAS.cdNa} Dp^Scer\UAS.cDa E2f⁹¹ E2f⁰⁷¹⁷² E2f^Scer\UAS.cNa eIF-4E⁰⁷²³⁸ gig^Scer\UAS.cTa gig^{ΔAkt-P.Scer\UAS.T:Zzzz\FLAG} Hsap\ATXN3^{tr.Q78.Scer\UAS.T:Ivir\HA1} Hsap\CDKN1A^Scer\UAS.cHa Hsap\MAPT^E14.Scer\UAS Hsap\MAPT^{R406W.Scer\UAS} Hsap\MAPT^Scer\UAS.cWa Hsap\MAPT^{V337M.Scer\UAS} Rbf^280.Scer\UAS Rbf^Scer\UAS.cDa Rheb^1.1.Scer\UAS Rheb^2D1 Rheb^AV4 rpr^Scer\UAS.C S6k⁰⁷⁰⁸⁴ S6k^l-1 Scer\GAL4^30Y Scer\GAL4^elav.PLu Scer\GAL4^{elav.Switch.PO} Scer\GAL4^GMR.PF sgg¹ Tor^2L7 Tor^2L15 Tor^k17004 Tsc1^Scer\UAS.cTa
Constructs (27)
	P{elav-Switch.O} P{GAL4-elav.L} P{GAL4-ninaE.GMR} P{UAS-cdc2.E51Q} P{UAS-cdc2.W} P{UAS-Cdk2-myc} P{UAS-Cdk4.M} P{UAS-CycA.W} P{UAS-CycB.W} P{UAS-CycD.M} P{UAS-CycE.U} P{UAS-dap.dN} P{UAS-Dp.D} P{UAS-E2f.N} P{UAS-gig.T} P{UAS-gig.ΔAkt-P.FLAG} P{UAS-Hsap\MAPT.E14} P{UAS-Hsap\MAPT.R406W} P{UAS-Hsap\MAPT.V337M} P{UAS-Hsap\MAPT.W} P{UAS-Hsap\MJD.tr-Q78} P{UAS-p21.H} P{UAS-Rbf.280} P{UAS-Rbf.D} P{UAS-Rheb.1.1} P{UAS-rpr.C} P{UAS-Tsc1.T}
Genes (26)
	cdc2 cdc2c Cdk4 CycA CycB CycB3 CycD CycE dap Dp E2f eIF-4E gig Hsap\ATXN3 Hsap\CDKN1A Hsap\MAPT Rbf Rheb rpr S6k Scer\GAL4 sgg tau Tor Tsc Tsc1
Insertions (2)
	P{GawB}30Y P{Mae-UAS.6.11}Rheb^AV4
Natural transposons (1)
	P-element