PDF(Pubmed)
Abstract：
Decades of research have identified genetic and environmental factors involved in age-related neurodegenerative diseases and, to a lesser extent, neuropsychiatric disorders. Genomic instability, i.e., the loss of genome integrity, is a common feature among both neurodegenerative (mayo-trophic lateral sclerosis, Parkinson\'s disease, Alzheimer\'s disease) and psychiatric (schizophrenia, autism, bipolar depression) disorders. Genomic instability is associated with the accumulation of persistent DNA damage and the activation of DNA damage response (DDR) pathways, as well as pathologic neuronal cell loss or senescence. Typically, DDR signaling ensures that genomic and proteomic homeostasis are maintained in both dividing cells, including neural progenitors, and post-mitotic neurons. However, dysregulation of these protective responses, in part due to aging or environmental insults, contributes to the progressive development of neurodegenerative and/or psychiatric disorders. In this Special Issue, we introduce and highlight the overlap between neurodegenerative diseases and neuropsychiatric disorders, as well as the emerging clinical, genomic, and molecular evidence for the contributions of DNA damage and aberrant DNA repair. Our goal is to illuminate the importance of this subject to uncover possible treatment and prevention strategies for relevant devastating brain diseases.
摘要：
几十年的研究已经确定了与年龄相关的神经退行性疾病的遗传和环境因素，在较小程度上，神经精神疾病。基因组不稳定,即，基因组完整性的丧失，是两种神经退行性疾病的共同特征(梅奥营养侧索硬化症，帕金森病,阿尔茨海默病）和精神病（精神分裂症，自闭症,双相抑郁）障碍。基因组不稳定性与持续DNA损伤的积累和DNA损伤反应（DDR）途径的激活有关，以及病理性神经元细胞丢失或衰老。通常,DDR信号确保基因组和蛋白质组稳态在两个分裂的细胞中保持。包括神经祖细胞，和有丝分裂后的神经元。然而,这些保护性反应的失调，部分原因是老化或环境侮辱，有助于神经退行性疾病和/或精神疾病的进行性发展。在这个特刊中,我们介绍并强调神经退行性疾病和神经精神疾病之间的重叠，以及新兴的临床，基因组，以及DNA损伤和异常DNA修复的分子证据。我们的目标是阐明这一主题的重要性，以发现相关破坏性脑疾病的可能治疗和预防策略。
