Maheshwari, M and Shekhar, S and Singh, BK and Jamal, I and Vatsa, N and Kimar, V and Sharma, A and Jana, NR (2014) Deficiency of Ube3a in Huntington's disease mice brain increases aggregate load and accelerates disease pathology. Hum Mol Genet, 23 (23). pp. 6235-6245.

Text 135_Deficiency of Ube3a in Huntington's disease mice brain increases aggregate load....pdf Restricted to Registered users only Download (1063Kb)

Abstract

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by abnormal expansion of CAG repeats in the gene encoding huntingtin. Mutant huntingtin undergoes proteolytic processing and its N-terminal fragment containing polyglutamine repeat accumulates as inclusion not only in nucleus but also in cytoplasm and neuronal processes. Here, we demonstrate that removal of ubiquitin ligase Ube3a selectively from HD mice brain resulted in accelerated disease phenotype and shorter lifespan in comparison with HD mice. The deficiency of Ube3a in HD mice brain also caused significant increase in global aggregates load, and these aggregates were less ubiquitinated when compared with age-matched HD mice. These Ube3a-maternal deficient HD mice also showed drastic reduction of DARPP-32, a dopamine-regulated phoshphoprotein in their striatum. These results emphasize the crucial role of Ube3a in the progression of HD and its immense potential as therapeutic target.

Item Type:	Article
Subjects:	Neurodegenerative Disorders Neuro-Oncological Disorders Neurocognitive Processes Neuronal Development and Regeneration Informatics and Imaging Genetics and Molecular Biology
Depositing User:	Mr D.D. Lal
Date Deposited:	07 Jul 2017 06:54
Last Modified:	08 Aug 2017 05:18
URI:	http://nbrc.sciencecentral.in/id/eprint/170

Actions (login required)

View Item