來自埃默里大學(xué)醫(yī)學(xué)院藥理學(xué)系,，阿拉伯馬州大學(xué)伯明翰分校的研究人員發(fā)現(xiàn)路易氏小體（Lewy bodies）與重要神經(jīng)元的健康與存活有著直接的作用,，這一發(fā)現(xiàn)有助于更好地理解帕金森氏癥和其它的神經(jīng)退行性疾病，改善對其的治療,。
之前的研究表明路易氏小體是α－突觸核蛋白（α－synuclein）由可溶性變?yōu)椴蝗苄援惓＞奂?。大多?shù)帕金森氏病的病例是散發(fā)的，說明沒有明顯的遺傳因素,，但也有遺傳形式的帕金森氏病,。一些遺傳形式的帕金森氏病與α-突觸核蛋白基因變異和三倍體基因有關(guān)。這兩種基因因素或者產(chǎn)生有毒性的α-突觸核蛋白,，或者產(chǎn)生較正常多的α-突觸核蛋白,。
研究人員利用轉(zhuǎn)基因和基因敲除的小鼠以及人類的腦組織來觀察分子伴侶介導(dǎo)自噬（CMA），他們發(fā)現(xiàn)CMA是以將某個特別的轉(zhuǎn)錄因子MEF2D（myocyte enhancer factor 2D ）作為標(biāo)靶來進行降解的,，由于這個MEF2D轉(zhuǎn)錄因子已經(jīng)被發(fā)現(xiàn)與數(shù)種類型的神經(jīng)元的存活有關(guān),，因此研究人員認為CMA在這些神經(jīng)元中與細胞核存活的細胞器有著直接的關(guān)聯(lián)。而且研究人員還發(fā)現(xiàn)α-突觸核蛋白對MEF2D的CMA的易化有幫助,，從而提出α-突觸核蛋白的聚集會干擾細胞的MEF2D循環(huán),，導(dǎo)致細胞死亡。（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 -synuclein transgenic mice and patients with Parkinson's disease. Wild-type -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.
