Effects and Mechanisms of Rapamycin Action on Experimental Neurodegeneration

被引:5
作者
Pupyshev, A. B. [1 ]
Korolenko, T. A. [1 ]
Tikhonova, M. A. [1 ,2 ]
机构
[1] Sci Res Inst Physiol & Basic Med, Novosibirsk, Russia
[2] Novosibirsk State Univ, Novosibirsk, Russia
基金
俄罗斯基础研究基金会;
关键词
neurodegeneration; neuroprotection; autophagy; rapamycin; mTOR; MOUSE MODEL; IN-VITRO; AUTOPHAGY INDUCTION; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; AMYLOID-BETA; NEURON DEATH; MTOR; INHIBITION; CLEARANCE;
D O I
10.1134/S1819712418030108
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Rapamycin is a strong inducer of autophagy which binds with its target protein mTOR and causes inhibition of biosynthetic and mitotic cell activities. The review considers neuroprotective properties of autophagy induction by rapamycin. The most important feature of the neurodegenerative diseases is the accumulation of specific proteins, such as amyloid-, -synuclein, huntingtin, etc. Their accumulation is associated with the weakening of the cellular function of the protein quality control provided by the ubiquitin-proteasomal system and autophagy, including chaperone-mediated autophagy. In many cases, activation of autophagy by rapamycin is able to restore the quality control of proteins and organelles, to attenuate the accumulation of pathogenic proteins. Mechanisms of rapamycin therapeutic effects include activation of the clearance of neurons from pathogenic material and induction of both autophagosomal segregation of cellular material and the lysosomal flux by activating TFEB factor, which is the inductor of the lysosomal biogenesis. Short-term treatment with rapamycin has a positive therapeutic effect in models of acute brain injury (trauma, ischemia, hypoxia). Inhibition of neurodegeneration requires long-term therapy. Neuroprotective effect of rapamycin is higher if started at young age. Good results are achieved by prolonged treatment with rapamycin in intermittent mode.
引用
收藏
页码:347 / 358
页数:12
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