來自埃默里大學醫(yī)學院藥理學系,，阿拉伯馬州大學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,。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自噬（CMA）,，他們發(fā)現(xiàn)CMA是以將某個特別的轉錄因子MEF2D（myocyte enhancer factor 2D ）作為標靶來進行降解的，由于這個MEF2D轉錄因子已經(jīng)被發(fā)現(xiàn)與數(shù)種類型的神經(jīng)元的存活有關,，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.
