Programa Doutoral em Biologia Experimental e Biomedicina, Centro de Neurociências e Biologia Celular, Coimbra, Portugal.
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Mar 30;35(2):348-55. doi: 10.1016/j.pnpbp.2010.08.008. Epub 2010 Aug 22.
Several diseases are known to have a multifactorial origin, depending not only on genetic but also on environmental factors. They are called "complex disorders" and include cardiovascular disease, cancer, diabetes, and neuropsychiatric and neurodegenerative diseases. In the latter class, Alzheimer's (AD) and Parkinson's diseases (PD) are by far the most common in the elderly and constitute a tremendous social and economical problem. Both disorders present familial and sporadic forms and although some polymorphisms and risk factors have been associated with AD and PD, the precise way by which the environment contributes to neurodegeneration is still unclear. Recent studies suggest that environmental factors may contribute for neurodegeneration through induction of epigenetic modifications, such as DNA methylation, and chromatin remodeling, which may induce alterations in gene expression programs. Epigenetics, which refers to any process that alters gene activity without changing the actual DNA sequence, and leads to modifications that can be transmitted to daughter cells, is a relatively novel area of research that is currently attracting a high level of interest. Epigenetic modulation is present since the prenatal stages, and the aging process is now accepted to be associated with a loss of phenotypic plasticity to epigenetic modifications. Since aging is the most important risk factor for idiopathic AD and PD, it is expected that epigenetic alterations on DNA and/or chromatin structure may also accumulate in neurodegeneration, accounting at least in part to the etiology of these disorders.
一些疾病的发生被认为具有多因素起源，不仅与遗传因素有关，还与环境因素有关。这些疾病被称为“复杂疾病”，包括心血管疾病、癌症、糖尿病以及神经精神和神经退行性疾病。在后一类疾病中，阿尔茨海默病（AD）和帕金森病（PD）在老年人中最为常见，是一个巨大的社会和经济问题。这两种疾病既有家族性也有散发性形式，尽管已经有一些多态性和危险因素与 AD 和 PD 相关，但环境导致神经退行性变的确切方式仍不清楚。最近的研究表明，环境因素可能通过诱导表观遗传修饰（如 DNA 甲基化和染色质重塑）而导致神经退行性变，这可能导致基因表达程序的改变。表观遗传学是指任何改变基因活性而不改变实际 DNA 序列的过程，并导致可传递给子细胞的修饰，这是一个相对较新的研究领域，目前正引起高度关注。表观遗传修饰从产前阶段就存在，衰老过程现在被认为与对表观遗传修饰的表型可塑性丧失有关。由于衰老是特发性 AD 和 PD 的最重要危险因素，因此预计 DNA 和/或染色质结构的表观遗传改变也可能在神经退行性变中积累，至少部分解释了这些疾病的病因。
