Autophagy in neurite injury and neurodegeneration: in vitro and in vivo models.
Autophagy in neurite injury and neurodegeneration: in vitro and in vivo models.
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DOI：
10.1016/s0076-6879(08)04011-1
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发表时间：
2009
影响因子：
--
通讯作者：
Clark, Robert S. B.
中科院分区：
文献类型：
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作者：
Chu, Charleen T.;Plowey, Edward D.;Dagda, Ruben K.;Hickey, Robert W.;Cherra, Salvatore J., III;Clark, Robert S. B.
最近的研究表明，维持平衡的自噬水平对神经元的健康和功能至关重要。巨噬的病理性失调与突触功能障碍、细胞应激和神经元细胞死亡有关。急性和慢性神经系统疾病包括中风、脑外伤、神经毒素损伤、帕金森病、阿尔茨海默病、亨廷顿病、运动神经元、朊病毒、溶酶体贮积和其他神经退行性疾病均可诱导自噬体和自溶酶体。与其他细胞类型相比，神经元自噬研究提出了特殊的挑战，可以通过仍在发展的技术来解决。神经元的功能取决于轴突和树突（统称为神经突）的维持，这些轴突和树突从细胞体延伸很远。自噬和线粒体含量都与神经突长度和生理（可塑性）和病理重塑功能的调节有关。在这里，我们重点介绍了几种分子细胞生物学和成像方法，以研究分化的神经元细胞系和原代神经元培养物的神经性和体细胞室中的自噬和有丝自噬，使用在帕金森神经变性的毒性和遗传模型中开发的方案。此外，成熟的神经元可以用体内模型来研究缺血性和创伤性损伤。未来的挑战包括将计算机辅助图像分析应用于单个神经元的轴突树，以及改进测量神经元自噬通量的方法。
Recent advances indicate that maintaining a balanced level of autophagy is critically important for neuronal health and function. Pathologic dysregulation of macroautophagy has been implicated in synaptic dysfunction, cellular stress, and neuronal cell death. Autophagosomes and autolysosomes are induced in acute and chronic neurological disorders including stroke, brain trauma, neurotoxin injury, Parkinson’s, Alzheimer’s, Huntington’s, motor neuron, prion, lysosomal storage, and other neurodegenerative diseases. Compared to other cell types, neuronal autophagy research presents particular challenges that may be addressed through still evolving techniques. Neuronal function depends upon maintenance of axons and dendrites (collectively known as neurites) that extend for great distances from the cell body. Both autophagy and mitochondrial content have been implicated in regulation of neurite length and function in physiological (plasticity) and pathological remodeling. Here, we highlight several molecular cell biological and imaging methods to study autophagy and mitophagy in neuritic and somatic compartments of differentiated neuronal cell lines and primary neuron cultures, using protocols developed in toxic and genetic models of parkinsonian neurodegeneration. In addition, mature neurons can be studied using in vivo protocols for modeling ischemic and traumatic injuries. Future challenges include application of automated computer-assisted image analysis to the axodendritic tree of individual neurons and improving methods for measuring neuronal autophagic flux.