据1月2日的《科学》杂志报道说,一种涉及某个细胞内容物的循环使用的过程对重要神经元的健康与存活有着直接的作用。这一发现可能会使人们更好地理解巴金森氏病和其它的神经退行性疾病,并可能改善对其的治疗。在一个被称作伴护介导自噬(或称“ CMA”)的过程中,一种细胞内的伴护物质会将某一特殊的蛋白质递交给溶酶体,而溶酶体则会在细胞内将该蛋白质的内容物分解并进行再循环。
Qian Yang及其同僚应用转基因和基因敲除的小鼠以及人类的脑组织来观察CMA。他们发现 CMA是以将某个特别的转录因子 MEF2D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,因此研究人员提出,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。他们还观察到, α-突触核蛋白(这是一种被认为与帕金森氏病的起病有关的蛋白)对MEF2D的CMA的易化具有帮助,这表明该通路将是一种治疗巴金森氏病及其它神经退行性疾病的可能的标靶。(生物谷Bioon.com)
生物谷推荐原始出处:
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 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.