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Age-related neurodegenerative diseases

机译:与年龄相关的神经退行性疾病

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Converging evidence indicates the dysregulation of unique cytosolic compartments called stress granules (SGs) might facilitate the accumulation of toxic protein aggregates that underlie many age-related neurodegenerative pathologies (ANPs). SG dynamics are particularly susceptible to the cellular conditions that are commonly induced by aging, including the elevation in reactive oxygen species and increased concentration of aggregate-prone proteins. In turn, the persistent formation of these compartments is hypothesized to serve as a seed for subsequent protein aggregation. Notably, the protein quality control (PQC) machinery responsible for inhibiting persistent SGs (e.g., Hsc70-BAG3) can become compromised with age, suggesting that the modulation of such PQC mechanisms could reliably inhibit pathological processes of ANPs. As exemplified in the context of accelerated aging syndromes (i.e., Hutchinson-Gilford progeria), PQC enhancement is emerging as a potential therapeutic strategy, indicating similar techniques might be applied to ANPs. Collectively, these recent findings advance our understanding of how the processes that might facilitate protein aggregation are particularly susceptible to aging conditions, and present investigators with an opportunity to develop novel targets for ANPs.
机译:融合证据表明的失调独特的胞质被称为压力的小隔间里颗粒(SGs)可能促进积累背后很多的有毒蛋白质聚合体与年龄相关的神经退行性疾病(anp)。SG动力学特别容易细胞通常引起的条件老化,包括活性氧的高程种类和浓度的增加aggregate-prone蛋白质。这些隔间是假设的形成为后续的蛋白作为种子聚合。(PQC)机械负责抑制持续的SGs(例如,Hsc70-BAG3)可以成为妥协随着年龄的增长,这表明调制的PQC机制可以可靠地抑制anp病理过程。比如在加速老化症状(例如,Hutchinson-Gilford早衰症),PQC增强作为一种新兴的潜力治疗策略,表明相似技术可能应用于anp。总的来说,这些最近的发现推动我们理解的过程如何促进蛋白质聚合尤其容易老化条件下,和现在调查人员与一个发展的机会anp的新目标。

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