Interplay Between the Autophagy-Lysosomal Pathway and the Ubiquitin-Proteasome System: A Target for Therapeutic Development in Alzheimer's Disease.
Interplay Between the Autophagy-Lysosomal Pathway and the Ubiquitin-Proteasome System: A Target for Therapeutic Development in Alzheimer's Disease.
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DOI：
10.3389/fncel.2018.00126
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发表时间：
2018
影响因子：
5.3
通讯作者：
Burgos PV
中科院分区：
文献类型：
--
作者：
Bustamante HA;González AE;Cerda-Troncoso C;Shaughnessy R;Otth C;Soza A;Burgos PV
阿尔茨海默病（AD）是年龄相关性痴呆的最常见原因，导致严重的不可逆的认知能力下降和大规模的神经退行性变。虽然用于管理症状的治疗方法是可用的，但AD目前没有治愈方法。AD与真核细胞的两个主要分解代谢途径-自噬-溶酶体途径（ALP）和泛素-蛋白酶体系统（UPS）-的进行性下降相关，这有助于参与突触可塑性和长期记忆障碍的有害分子的积累。淀粉样前体蛋白（APP）胞内C-末端膜片段β（CTFβ）是最近被强调为这些紊乱的最早引发剂的一种蛋白质，其是对神经元功能具有有害作用的关键毒性剂，已成为AD的重要致病因素和AD患者的潜在生物标志物。本文综述了参与调节分子和特定的翻译后修饰（PTM），在UPS和ALP控制一个单一的蛋白质平衡网络，以实现蛋白质平衡。我们讨论了这些方面如何有助于开发新的策略，以加强与AD相关的关键致病蛋白的平衡。
Alzheimer’s disease (AD) is the most common cause of age-related dementia leading to severe irreversible cognitive decline and massive neurodegeneration. While therapeutic approaches for managing symptoms are available, AD currently has no cure. AD associates with a progressive decline of the two major catabolic pathways of eukaryotic cells—the autophagy-lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS)—that contributes to the accumulation of harmful molecules implicated in synaptic plasticity and long-term memory impairment. One protein recently highlighted as the earliest initiator of these disturbances is the amyloid precursor protein (APP) intracellular C-terminal membrane fragment β (CTFβ), a key toxic agent with deleterious effects on neuronal function that has become an important pathogenic factor for AD and a potential biomarker for AD patients. This review focuses on the involvement of regulatory molecules and specific post-translational modifications (PTMs) that operate in the UPS and ALP to control a single proteostasis network to achieve protein balance. We discuss how these aspects can contribute to the development of novel strategies to strengthen the balance of key pathogenic proteins associated with AD.
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Johansen, Terje
DOI：
10.1083/jcb.201002108
发表时间：
2010-08-23
期刊：
The Journal of cell biology
影响因子：
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作者：
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