Sulzer David, Mosharov Eugene, Talloczy Zsolt, Zucca Fabio A, Simon John D, Zecca Luigi
Department of Neurology, Columbia University, New York, NY 10036, USA.
J Neurochem. 2008 Jul;106(1):24-36. doi: 10.1111/j.1471-4159.2008.05385.x. Epub 2008 Apr 1.
The most striking morphologic change in neurons during normal aging is the accumulation of autophagic vacuoles filled with lipofuscin or neuromelanin pigments. These organelles are similar to those containing the ceroid pigments associated with neurologic disorders, particularly in diseases caused by lysosomal dysfunction. The pigments arise from incompletely degraded proteins and lipids principally derived from the breakdown of mitochondria or products of oxidized catecholamines. Pigmented autophagic vacuoles may eventually occupy a major portion of the neuronal cell body volume because of resistance of the pigments to lysosomal degradation and/or inadequate fusion of the vacuoles with lysosomes. Although the formation of autophagic vacuoles via macroautophagy protects the neuron from cellular stress, accumulation of pigmented autophagic vacuoles may eventually interfere with normal degradative pathways and endocytic/secretory tasks such as appropriate response to growth factors.
在正常衰老过程中，神经元最显著的形态学变化是充满脂褐素或神经黑色素的自噬空泡的积累。这些细胞器类似于那些含有与神经系统疾病相关的类蜡样色素的细胞器，特别是在由溶酶体功能障碍引起的疾病中。这些色素主要来源于未完全降解的蛋白质和脂质，主要来自线粒体的分解或氧化儿茶酚胺的产物。由于色素对溶酶体降解具有抗性和/或空泡与溶酶体的融合不足，有色素的自噬空泡最终可能占据神经元细胞体体积的大部分。尽管通过巨自噬形成自噬空泡可保护神经元免受细胞应激，但有色素的自噬空泡的积累最终可能会干扰正常的降解途径以及内吞/分泌任务，如对生长因子的适当反应。
