Migliore Lucia, Coppedè Fabio
Dipartimento di Scienze dell'Uomo e dell'Ambiente, University of Pisa, via S. Giuseppe 22, 56126, Pisa, Italy.
Mutat Res. 2002 Dec;512(2-3):135-53. doi: 10.1016/s1383-5742(02)00046-7.
The aim of this review is to summarise the recent findings in the fields of carcinogenesis and neurodegenerative diseases, the both disorders are characterised by the contribution of different factors including the inheritance of mutated genes, and the exposure to endogenous or exogenous agents during the life. We first analysed the causative genes until now discovered in both processes, then we focused our attention on the role of environmental exposure, susceptibility factors, oxidative stress, apoptosis and aging to the development of such disorders. The genotype at a particular locus may account for an inter-individual susceptibility that can both increase or decrease the risk to develop the pathology especially after the exposure to environmental agents. The mechanism of apoptosis, that is an excellent strategy in order to eliminate damaged cells, seems to be lost during carcinogenesis, while it seems to be involved in the neuronal death in a lot of neurodegenerative disorders. Oxidative stress can both lead to DNA mutations or to the formation of damaged proteins, so being an important risk factor for the initiation and the progression of a disease: in fact it may be one of the causes or can arise as a consequence of a damage caused by other factors increasing then the first damage. It is well established that carcinogenesis is a multi-step process caused by series of successive mutations occurring into a cell and conferring to this cell a growth advantage, so that age is the largest risk factor for cancer in humans. Pathophysiology of neurodegenerative diseases is complex and likely involves multiple overlapping and perhaps redundant pathways of neuronal damage, characterised by the generation of anomalous proteins, often due to mutations in the corresponding gene, and by their subsequent accumulation into or outside specific areas of the brain.
本综述的目的是总结癌症发生和神经退行性疾病领域的最新研究结果。这两种疾病的特征是由不同因素导致的，包括突变基因的遗传以及生命过程中内源性或外源性因素的暴露。我们首先分析了到目前为止在这两个过程中发现的致病基因，然后将注意力集中在环境暴露、易感性因素、氧化应激、细胞凋亡和衰老在这些疾病发展中的作用上。特定基因座的基因型可能解释个体间的易感性，这种易感性可能增加或降低患病理疾病的风险，尤其是在接触环境因素之后。细胞凋亡机制是清除受损细胞的一种极佳策略，在癌症发生过程中似乎丧失了作用，而在许多神经退行性疾病中，它似乎与神经元死亡有关。氧化应激既可能导致DNA突变，也可能导致受损蛋白质的形成，因此是疾病发生和进展的重要危险因素：事实上，它可能是病因之一，也可能是其他因素造成损伤的结果，进而加剧最初的损伤。众所周知，癌症发生是一个多步骤过程，由细胞中一系列连续发生的突变引起，并赋予该细胞生长优势，因此年龄是人类患癌症的最大风险因素。神经退行性疾病的病理生理学很复杂，可能涉及神经元损伤的多个重叠甚至冗余途径，其特征是异常蛋白质的产生，这通常是由于相应基因突变所致，以及这些蛋白质随后在大脑特定区域内或外的积累。
