来自埃默里大学医学院药理学系，阿拉伯马州大学伯明翰分校的研究人员发现路易氏小体（Lewy bodies）与重要神经元的健康与存活有着直接的作用，这一发现有助于更好地理解帕金森氏症和其它的神经退行性疾病，改善对其的治疗。

之前的研究表明路易氏小体是α－突触核蛋白（α－synuclein）由可溶性变为不溶性异常聚集而成。大多数帕金森氏病的病例是散发的，说明没有明显的遗传因素，但也有遗传形式的帕金森氏病。一些遗传形式的帕金森氏病与α-突触核蛋白基因变异和三倍体基因有关。这两种基因因素或者产生有毒性的α-突触核蛋白，或者产生较正常多的α-突触核蛋白。

研究人员利用转基因和基因敲除的小鼠以及人类的脑组织来观察分子伴侣介导自噬（CMA），他们发现CMA是以将某个特别的转录因子MEF2D（myocyte enhancer factor 2D ）作为标靶来进行降解的，由于这个MEF2D转录因子已经被发现与数种类型的神经元的存活有关，因此研究人员认为CMA在这些神经元中与细胞核存活的细胞器有着直接的关联。而且研究人员还发现α-突触核蛋白对MEF2D的CMA的易化有帮助，从而提出α-突触核蛋白的聚集会干扰细胞的MEF2D循环，导致细胞死亡。

推荐原始出处：

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.