Proteolytic mechanisms have been implicated in the process of ageing, and in many neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases, which are most prevalent in old age. Simple model organisms such as the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, which offer the prowess of sophisticated genetic approaches, have contributed to our understanding of ageing and neurodegeneration. Intensive research in these systems has resulted in detailed models of the ageing process, and also of several neurodegenerative diseases, which recapitulate same aspects of the human pathologies. Inappropriate cell death is a major component of these and other devastating conditions such as stroke. The dissection of the molecular mechanisms underlying the process of cell degeneration in ageing is of utmost importance. Evidence from investigations in C. elegans implicates deregulated proteolysis as one major determinant of cellular destruction in neurodegeneration and ageing, and suggests that the process depends critically on the activation of calcium-dependent, calpain proteases and lysosomal aspartyl proteases. Apart from shedding light on important but inadequately understood facets of such phenomena, these discoveries hold promise for developing novel, effective intervention strategies aiming to ameliorate or even counter inappropriate cell death.

中文翻译：

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钙依赖和天冬氨酰蛋白酶在秀丽隐杆线虫的神经变性和衰老中。

蛋白水解机制与衰老过程以及许多神经退行性疾病如老年痴呆症有关，例如老年痴呆，帕金森氏症和亨廷顿氏症。简单的模型生物，例如线虫秀丽隐杆线虫和果蝇果蝇（Drosophila melanogaster），它们提供了复杂的遗传方法的能力，有助于我们理解衰老和神经退行性变。在这些系统中的深入研究得出了衰老过程以及几种神经退行性疾病的详细模型，这些模型概括了人类病理学的相同方面。不适当的细胞死亡是这些和其他破坏性疾病（例如中风）的主要组成部分。解剖衰老过程中细胞变性过程的分子机制至关重要。秀丽隐杆线虫研究的证据表明，蛋白水解失调是神经变性和衰老过程中细胞破坏的一个主要决定因素，并表明该过程主要取决于钙依赖性钙蛋白酶，钙蛋白酶和溶酶体天冬氨酰蛋白酶的活化。除了揭示这些现象的重要但未被充分理解的方面外，这些发现还有望开发出新颖，有效的干预策略，旨在改善甚至应对不适当的细胞死亡。并表明该过程主要取决于钙依赖性钙蛋白酶蛋白酶和溶酶体天冬氨酰蛋白酶的活化。除了揭示这些现象的重要但未被充分理解的方面外，这些发现还有望开发出新颖，有效的干预策略，旨在改善甚至应对不适当的细胞死亡。并表明该过程主要取决于钙依赖性钙蛋白酶蛋白酶和溶酶体天冬氨酰蛋白酶的活化。除了揭示这些现象的重要但未被充分理解的方面外，这些发现还有望开发出新颖，有效的干预策略，旨在改善甚至应对不适当的细胞死亡。