2012年12月6日訊 /生物谷BIOON/ --一項研究在細胞水平上了解了神經(jīng)退行性疾病如帕金森氏癥,，阿爾茨海默氏癥和亨廷頓氏病的發(fā)生發(fā)展過程,，對打擊這類疾病帶來了一個新的認識。
神經(jīng)退行性疾病導致運動功能或認知功能或兩者降低,，這是由大腦的特定區(qū)域負責這些功能退化導致的,。
雖然這些功能與神經(jīng)退行性疾病毒蛋白聚合有關，但有很多是機制如在細胞水平上哪種聚合引起神經(jīng)毒性和死亡是未知的,。由致病蛋白質(zhì)聚集的結構包涵體長期被視為一個疾病的標志性物質(zhì),，但包涵體和疾病之間的關系一直有些神秘。
在一項發(fā)表在PNAS雜志上研究中,，這些歷來被認為伴隨著疾病發(fā)生的包涵體,，實際上有一個與疾病沒有必然聯(lián)系的細胞生物功能。
此外,，研究人員認為這些包涵體不僅是沒有毒性的,，實際上還發(fā)揮一種天然保護機制。研究人員已經(jīng)確定了兩個包涵體 JUNQ和IPOD,。在JUNQ中蛋白聚集可能會導致毒性,，而聚集在IPOD中則會發(fā)揮保護作用。
希伯來大學研究人員說,，這些研究結果指出了一個新的潛在的戰(zhàn)略治療神經(jīng)退行性疾病,。取代非常困難的防止蛋白聚合的方法，封閉包涵體有害蛋白聚集的能力,，從而中和進一步導致神經(jīng)退行性損傷的有毒蛋白質(zhì),。（生物谷：Bioon.com）
doi:10.1073/pnas.1205829109
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Compartmentalization of superoxide dismutase 1 (SOD1G93A) aggregates determines their toxicity.
S. J. Weisberg, R. Lyakhovetsky, A.-c. Werdiger, A. D. Gitler, Y. Soen, D. Kaganovich.
Neurodegenerative diseases constitute a class of illnesses marked by pathological protein aggregation in the brains of affected individuals. Although these disorders are invariably characterized by the degeneration of highly specific subpopulations of neurons, protein aggregation occurs in all cells, which indicates that toxicity arises only in particular cell biological contexts. Aggregation-associated disorders are unified by a common cell biological feature: the deposition of the culprit proteins in inclusion bodies. The precise function of these inclusions remains unclear. The starting point for uncovering the origins of disease pathology must therefore be a thorough understanding of the general cell biological function of inclusions and their potential role in modulating the consequences of aggregation. Here, we show that in human cells certain aggregate inclusions are active compartments. We find that toxic aggregates localize to one of these compartments, the juxtanuclear quality control compartment (JUNQ), and interfere with its quality control function. The accumulation of SOD1G93A aggregates sequesters Hsp70, preventing the delivery of misfolded proteins to the proteasome. Preventing the accumulation of SOD1G93A in the JUNQ by enhancing its sequestration in an insoluble inclusion reduces the harmful effects of aggregation on cell viability.
