小腦萎縮症病友協會

袁志道先生多年來提供獎學金，鼓勵研究生發表小腦萎縮症國際研討會的論文，現在成果豐碩，已轟動全世界的醫學界，是袁志道先生的遠見。
袁志道先生是台灣的光榮。小腦萎縮症協會與有榮焉。台灣以他為榮！

2012 .2.10 轟動全世界醫學界 spt4 蛋白質 (小腦萎縮症的幫兇蛋白)研究論文   
陽明大學化生博士生    劉珈榮   參加第三屆小腦萎縮症國際研討會的論文

Spt4 down-regulation suppresses the expression of
CAG expanded genes that
encode aggregation-prone polypeptides
Chia-Rung Liu, Tzu-Hao Cheng
Institute of Biochemistry and Molecular Biology, National Yang-Ming University
劉珈榮
國立陽明大學生化暨分子生物研究所五年級
N9 neurodegenerative disorders are caused by CAG expansion in the coding sequence
of affected genes, including Huntington’s disease (HD) as well as Spinocerebellar ataxias
type 1, 2, 3, 6, 7, and 17. CAG repeats encode polyglutamine (polyQ) stretch and protein
with extended polyQ (>39Q) has a propensity to aggregate. The mutant proteins thus are
found to be the major component of proteinaceous deposits in patient’s brain and substantial
evidences indicate that the formation of insoluble polyQ aggregates is a main trigger for the
death of neuronal cells.
In this study, we have established an assay system to identify the gene mutation that
can relieve polyQ aggregation in yeast cells. Through genome-wide screening, we found
polyQ aggregation is decreased in spt4 deficient cells. The change was due to reduced level
of aggregation-prone proteins, and this was resulting from the suppressed expression of
corresponding genes at the level of transcription. Importantly, the transcription inhibitory
effect only occurred in the reporter genes with expanded CAG repeats, but not the
counterpart ones having a short stretch of CAG. Spt4 is a transcription elongation factor
and its function is highly conserved between mammalian and yeast cells. We also found
the expression of exogenous as well as endogenous gene with a long stretch of CAG is
selectively inhibited by the reduction of Spt4 in mouse neuron cells. Our findings therefore
suggested Spt4 is a pivotal regulator for the transcription of genes with a highly repetitive
CAG sequence and it may serve as a novel target for the neurological diseases that are
caused by expanded CAG trinucleotide repeats.

 (轉載自第三屆小腦萎縮症國際研討會大會手冊收藏論文NO.37)