Journal article

CO-REGULATION OF SURVIVAL OF MOTOR NEURON AND BCL-XL EXPRESSION: IMPLICATIONS FOR NEUROPROTECTION IN SPINAL MUSCULAR ATROPHY

RS Anderton, LL Price, BJ Turner, BP Meloni, C Mitrpant, FL Mastaglia, C Goh, SD Wilton, S Boulos

NEUROSCIENCE | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2012

Abstract

Spinal muscular atrophy (SMA), a fatal genetic motor disorder of infants, is caused by diminished full-length survival of motor neuron (SMN) protein levels. Normally involved in small nuclear ribonucleoprotein (snRNP) assembly and pre-mRNA splicing, recent studies suggest that SMN plays a critical role in regulating apoptosis. Interestingly, the anti-apoptotic Bcl-x isoform, Bcl-xL, is reduced in SMA. In a related finding, Sam68, an RNA-binding protein, was found to modulate splicing of SMN and Bcl-xL transcripts, promoting SMNΔ7 and pro-apoptotic Bcl-xS transcripts. Here we demonstrate that Bcl-xL expression increases SMN protein by ∼2-fold in SH-SY5Y cells. Conversely, SMN expression incre..

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