Neuroprotective modulation of the unfolded protein response in Marinesco-Sj?gren syndrome: PERK signaling inhibition and beyond

Individuals with Marinesco-Sj?gren syndrome(MSS;OMIM 248800),a genetic disease of infancy,suffer various disabilities,including loss of motor coordination due to cerebellar degeneration,and skeletal muscle weakness.After a progressive phase,symptoms stabilize and patients live to old age.Therefore,any pharmacological treatment that delays or attenuates cerebellar degeneration and/or muscle pathology can significantly improve their quality of life.We recently found that inhibiting the protein kinase RNA-like endoplasmic reticulum

Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

杂交技术修复胸腹主动脉瘤视频介绍

虽然开放胸腹主动脉(TAAA)修复术在最近的几十年中已取得很大发展,但目前Inclusion技术的并发症率及病死率仍较高,这对我们而言依旧是一个技术上的挑战,尤其是合并广泛的动脉瘤病变、既往有主动脉手术史以及非最佳手术指证的患者更是如此。杂交技术修复TAAA是一个研究热点,由于我们需要更大数量的可重复性结果来观察完全通过开窗和分支支架修复TAAA的可行性,因此杂交手术的经验在此期间起到了一种"桥梁"作用。