Reference Report

Reference
Citation	Elden, A.C., Kim, H.J., Hart, M.P., Chen-Plotkin, A.S., Johnson, B.S., Fang, X., Armakola, M., Geser, F., Greene, R., Lu, M.M., Padmanabhan, A., Clay-Falcone, D., McCluskey, L., Elman, L., Juhr, D., Gruber, P.J., Rub, U., Auburger, G., Trojanowski, J.Q., Lee, V.M., Van Deerlin, V.M., Bonini, N.M., Gitler, A.D. (2010). Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 466(7310): 1069--1075. (Export to RIS)
FlyBase ID	FBrf0214156
Publication Type	Research paper
PubMed ID	20740007
PubMed Abstract	The causes of amyotrophic lateral sclerosis (ALS), a devastating human neurodegenerative disease, are poorly understood, although the protein TDP-43 has been suggested to have a critical role in disease pathogenesis. Here we show that ataxin 2 (ATXN2), a polyglutamine (polyQ) protein mutated in spinocerebellar ataxia type 2, is a potent modifier of TDP-43 toxicity in animal and cellular models. ATXN2 and TDP-43 associate in a complex that depends on RNA. In spinal cord neurons of ALS patients, ATXN2 is abnormally localized; likewise, TDP-43 shows mislocalization in spinocerebellar ataxia type 2. To assess the involvement of ATXN2 in ALS, we analysed the length of the polyQ repeat in the ATXN2 gene in 915 ALS patients. We found that intermediate-length polyQ expansions (27-33 glutamines) in ATXN2 were significantly associated with ALS. These data establish ATXN2 as a relatively common ALS susceptibility gene. Furthermore, these findings indicate that the TDP-43-ATXN2 interaction may be a promising target for therapeutic intervention in ALS and other TDP-43 proteinopathies.
DOI	10.1038/nature09320
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Nature
Title	Nature
Publication Year	1869-
ISBN/ISSN	0028-0836
Data from Reference
Alleles (10)
	Atx2^EP3145 Atx2^X1 Avic\GFP^Scer\UAS.cUa Hsap\TARDBP^{Q331K.Scer\UAS} Hsap\TARDBP^Scer\UAS.cEa Hsap\TARDBP^{Scer\UAS.T:Avic\GFP-YFP} Scer\GAL4^D42 Scer\GAL4^elav-C155 Scer\GAL4^GMR.PF T:Avic\GFP^YFP
Constructs (5)
	P{GAL4-ninaE.GMR} P{UAS-GFP.U} P{UAS-TDP-43.Q331K} P{UAS-TDP-43.YFP} P{UAS-TDP-43}
Genes (7)
	Atx2 Avic\GFP Ecol\lacZ Hsap\ATXN3 Hsap\HSPA1L Hsap\TARDBP Scer\GAL4
Insertions (3)
	P{EP}Atx2^EP3145 P{GawB}D42 P{GawB}elav^C155
Natural transposons (1)
	P-element