<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Roshan, Reema</style></author><author><style face="normal" font="default" size="100%">Ghosh, Tanay</style></author><author><style face="normal" font="default" size="100%">Gadgil, Mugdha</style></author><author><style face="normal" font="default" size="100%">Pillai, Beena</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Regulation of BACE1 by miR-29a/b in a cellular model of spinocerebellar ataxia 17</style></title><secondary-title><style face="normal" font="default" size="100%">RNA Biology</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">BACE1</style></keyword><keyword><style  face="normal" font="default" size="100%">miR-29a/b</style></keyword><keyword><style  face="normal" font="default" size="100%">neurodegeneration</style></keyword><keyword><style  face="normal" font="default" size="100%">SCA17</style></keyword><keyword><style  face="normal" font="default" size="100%">TBP</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">JUN</style></date></pub-dates></dates><number><style face="normal" font="default" size="100%">6, SI</style></number><publisher><style face="normal" font="default" size="100%">LANDES BIOSCIENCE</style></publisher><pub-location><style face="normal" font="default" size="100%">1806 RIO GRANDE ST, AUSTIN, TX 78702 USA</style></pub-location><volume><style face="normal" font="default" size="100%">9</style></volume><pages><style face="normal" font="default" size="100%">891-899</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Polyglutamine diseases are a class of neurodegenerative disorders characterized by expansion of polyglutamine repeats, protein aggregation and neuronal cell death in specific regions of the brain. The expansion of a polyglutamine repeat in the TATA binding protein (TBP) causes a neurodegenerative disease, Spinocerebellar Ataxia 17 (SC A17). This disease is characterized by intranuclear protein aggregates and selective loss of cerebellar neurons, including Purkinje cells. MicroRNAs are small, endogenous, regulatory non-coding RNA molecules that bind to mRNAs with partial complementarity and interfere in their expression. Here, we used a cellular model of SC A17 where we expressed TBP with 16 (normal) or 59 (pathogenic) polyglutamines and found differential expression of several microRNAs. Specifically, we found two microRNAs, miR-29a/b, were downregulated. With miR-29a/b downregulation, we found an increased expression of targets of miR-29a/b-beta-site amyloid precursor protein cleaving enzyme 1 (BACE 1), p53 upregulated modulator of apoptosis (PUMA) and BAK, increased cytochrome c release and apoptosis. Restoration of miR-29a/b in the pathogenic polyglutamine background reduced the BACE 1 expression. While, antagomiRs against miR-29a/b resulted in an increase in BACE 1 levels and neuronal apoptosis. In spite of the elevation of BACE 1 in Alzhemiers disease, its role in neuronal cell death has not been established. Here, we show that increased BACE 1 expression is not sufficient to cause apoptosis. However restoring level of BACE 1 to normal in polyglutamine cells partially reduced neuronal apoptosis. We show a role for the miR-29a/b-BACE 1 regulatory interaction in SC A17, suggesting that this microRNA could be part of a common molecular mechanism leading to neuronal cell death in multiple neurodegenerative disorders. The identification of a common mechanism of microRNA mediated neurodegeneration not only improves our understanding of the process, but also provides promising and novel therapeutic targets.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">6</style></issue><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">4.841
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