Protein involved in Alzhe熱化imer's disease 厭了tau neurotoxici低區ty identified

Latest Discovery   |   Nov 29, 2022

Alzheimer's disease is the mos視上t common type of dementia and aff美醫ects ~55 million people worldwide. 師窗Aggregation of tau is a de路黃fining feature of Alzheimer’s disea器微se. Recently, research店知ers at the Indiana Un友工iversity School of Medicine ide廠飛ntified Bassoon, a scaff農師olding protein fou議跳nd in the brain, as an i上討nteractor and stabilizer of tau 朋書seeds.

The research team at the Indiana Uni林短versity School of Medicine led紙歌 by Dr. Cristian Lasagna-Ree快得ves and Dr. Pablo M頻煙artinez performed unb區玩iased quantitative proteomics to ident視煙ify interactors of tau seeds. After id森裡entifying Bassoon as an 章光interactor, the team went on to舞舊 show that it is 訊森also involved in 吧村tau neurotoxicity in Dro子拿sophila and mouse models.腦河

“Our paper established that a small 去鄉portion of tau is capable 為窗of propagating in human tauopathies, in的電cluding Alzheimer朋場’s disease. This small porti那唱on of tau, which repres女腦ent no more than兵分 8% of total tau i頻朋n the brain, interacts with員女 the presynaptic pro得森tein Bassoon, which enhances the p嗎電ropagating and seeding pr員報operties of tau and also大費 stabilizes toxic tau aggregates”, 間時said Dr. Pablo Martinez.

Dr. Martinez and his colleagues utilize化拍d Adeno-associated virus (AAV那北) and vectors p麗自roduced at VectorBuilde們窗r. Construction of the AAV vecto白國rs and AAV packaging was enabled by Vec雪內torBuilder’s Vector Design S爸能tudio. VectorBuilder of答雜fers superior qual森兵ity AAV single-stranded and self-comple路間mentary vector 體朋cloning and pa拍黑ckaging fo慢不r your research and c地多linical needs.

“I have been working視那 with VectorBuilder from暗快 the beginning of my postdoc. I’ve ch近時osen VB because of the online platform生討 to create customized vectors. 風生It is really impressive ho員作w easy it is to子術 digitally clone 下腦and the order process.&美鐘nbsp;Specifically, in our paper, we’ve就民 used VB for several critic有舊al experiments, including the會很 downregulation of Bassoon pro自筆tein (AAV-shRNA) and to 舊鐘study the role of Bassoon in the pro生站pagation of tau (分船AAV-GFP-P2A-hTau). These experi遠電ments were extremely 弟飛important to probe our hy議醫pothesis”, Dr. 照年Martinez further elaborated.

Overall, this study provides insight in作懂to the mechanism of neuro玩匠toxicity in Alzh友近eimer’s disease and other tauopathi在制es and could translate into ta身算rgeted therapies in 動人the future.  

Source: Martinez, P., Patel, H., 雨鐵You, Y. et al. Bas靜物soon contributes to 放學tau-seed propagation and neur藍可otoxicity. Nat Neurosci (202民費2).

https://doi.org子船/10.1038/s41593-022-01191-6

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