2012年12月6日訊 /生物谷BIOON/ --一項(xiàng)研究在細(xì)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(guò)程,，對(duì)打擊這類疾病帶來(lái)了一個(gè)新的認(rèn)識(shí),。
神經(jīng)退行性疾病導(dǎo)致運(yùn)動(dòng)功能或認(rèn)知功能或兩者降低，這是由大腦的特定區(qū)域負(fù)責(zé)這些功能退化導(dǎo)致的。
雖然這些功能與神經(jīng)退行性疾病毒蛋白聚合有關(guān)，但有很多是機(jī)制如在細(xì)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(jié)構(gòu)包涵體長(zhǎng)期被視為一個(gè)疾病的標(biāo)志性物質(zhì),，但包涵體和疾病之間的關(guān)系一直有些神秘,。
在一項(xiàng)發(fā)表在PNAS雜志上研究中，這些歷來(lái)被認(rèn)為伴隨著疾病發(fā)生的包涵體,，實(shí)際上有一個(gè)與疾病沒(méi)有必然聯(lián)系的細(xì)胞生物功能,。
此外，研究人員認(rèn)為這些包涵體不僅是沒(méi)有毒性的,，實(shí)際上還發(fā)揮一種天然保護(hù)機(jī)制,。研究人員已經(jīng)確定了兩個(gè)包涵體 JUNQ和IPOD。在JUNQ中蛋白聚集可能會(huì)導(dǎo)致毒性,，而聚集在IPOD中則會(huì)發(fā)揮保護(hù)作用,。
希伯來(lái)大學(xué)研究人員說(shuō)，這些研究結(jié)果指出了一個(gè)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(jìn)一步導(dǎo)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
PMC:
PMID:
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.
