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The intersection between growth factors, autophagy and ER stress: A new target to treat neurodegenerative diseases?

机译:生长因子,自噬和内质网应激之间的交集:治疗神经退行性疾病的新目标?

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摘要

One of the salient features of most neurodegenerative diseases is the aggregation of specific proteins in the brain. This proteostasis imbalance is proposed as a key event triggering the neurodegenerative cascade. The unfolded protein response (UPR) and autophagy pathways are emerging as critical processes implicated in handling disease-related misfolded proteins. However, in some conditions, perturbations in the buffering capacity of the proteostasis network may be part of the etiology of the disease. Thus, pharmacological or gene therapy strategies to enhance autophagy or UPR responses are becoming an attractive target for disease intervention. Here, we discuss current evidence depicting the complex involvement of autophagy and ER stress in brain diseases. Novel pathways to modulate protein misfolding are discussed including the relation between aging and growth factor signaling. This article is part of a Special Issue entitled SI:Autophagy. (C) 2016 Elsevier B.V. All rights reserved.
机译:大多数神经退行性疾病的显着特征之一是大脑中特定蛋白质的聚集。这种蛋白稳态失衡被认为是触发神经变性级联反应的关键事件。折叠蛋白反应(UPR)和自噬途径正在作为涉及疾病相关错折叠蛋白的关键过程而出现。然而,在某些情况下,蛋白稳态网络缓冲能力的扰动可能是该病因的一部分。因此,增强自噬或UPR反应的药理或基因治疗策略正成为疾病干预的有吸引力的目标。在这里,我们讨论了目前的证据,这些证据描述了自噬和内质网应激在脑部疾病中的复杂参与。讨论了调节蛋白质错误折叠的新途径,包括衰老和生长因子信号传导之间的关系。本文是标题为SI:Autophagy的特刊的一部分。 (C)2016 Elsevier B.V.保留所有权利。

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