據(jù)1月2日的《科學(xué)》雜志報(bào)道說(shuō),，一種涉及某個(gè)細(xì)胞內(nèi)容物的循環(huán)使用的過(guò)程對(duì)重要神經(jīng)元的健康與存活有著直接的作用,。這一發(fā)現(xiàn)可能會(huì)使人們更好地理解巴金森氏病和其它的神經(jīng)退行性疾病，并可能改善對(duì)其的治療,。在一個(gè)被稱(chēng)作伴護(hù)介導(dǎo)自噬（或稱(chēng)“ CMA”）的過(guò)程中,，一種細(xì)胞內(nèi)的伴護(hù)物質(zhì)會(huì)將某一特殊的蛋白質(zhì)遞交給溶酶體，而溶酶體則會(huì)在細(xì)胞內(nèi)將該蛋白質(zhì)的內(nèi)容物分解并進(jìn)行再循環(huán),。
Qian Yang及其同僚應(yīng)用轉(zhuǎn)基因和基因敲除的小鼠以及人類(lèi)的腦組織來(lái)觀(guān)察CMA,。他們發(fā)現(xiàn) CMA是以將某個(gè)特別的轉(zhuǎn)錄因子 MEF2D作為標(biāo)靶來(lái)進(jìn)行降解的。由于這個(gè) MEF2D轉(zhuǎn)錄因子已經(jīng)被發(fā)現(xiàn)與數(shù)種類(lèi)型的神經(jīng)元的存活有關(guān),，因此研究人員提出,，CMA在這些神經(jīng)元中與細(xì)胞核存活的細(xì)胞器有著直接的關(guān)聯(lián)。他們還觀(guān)察到,， α-突觸核蛋白（這是一種被認(rèn)為與帕金森氏病的起病有關(guān)的蛋白）對(duì)MEF2D的CMA的易化具有幫助,，這表明該通路將是一種治療巴金森氏病及其它神經(jīng)退行性疾病的可能的標(biāo)靶。（生物谷Bioon.com）
生物谷推薦原始出處：
Science 2 January 2009: DOI: 10.1126/science.1166088
Regulation of Neuronal Survival Factor MEF2D by Chaperone-Mediated Autophagy
Qian Yang,1 Hua She,1 Marla Gearing,2 Emanuela Colla,3 Michael Lee,3 John J. Shacka,4 Zixu Mao1,2*
Chaperone-mediated autophagy controls the degradation of selective cytosolic proteins and may protect neurons against degeneration. In a neuronal cell line, we found that chaperone-mediated autophagy regulated the activity of myocyte enhancer factor 2D (MEF2D), a transcription factor required for neuronal survival. MEF2D was observed to continuously shuttle to the cytoplasm, interact with the chaperone Hsc70, and undergo degradation. Inhibition of chaperone-mediated autophagy caused accumulation of inactive MEF2D in the cytoplasm. MEF2D levels were increased in the brains of α-synuclein transgenic mice and patients with Parkinson's disease. Wild-type α-synuclein and a Parkinson's disease–associated mutant disrupted the MEF2D-Hsc70 binding and led to neuronal death. Thus, chaperone-mediated autophagy modulates the neuronal survival machinery, and dysregulation of this pathway is associated with Parkinson's disease.
1 Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
2 Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
3 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
4 Department of Pathology, Division of Neuropathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
