摘要
Reactive oxygen species have been implicated in conditions ranging from cardiovascular dysfunc- tion, arthritis, cancer, to aging and age-related disorders. The organism developed several path- ways to counteract these effects, with base excision repair being responsible for repairing one of the major base lesions （8-oxoG） in all organisms. Epidemiological evidence suggests that cognitive stimulation makes the brain more resilient to damage or degeneration. Recent studies have linked enriched environment to reduction of oxidative stressin neurons of mice with Alzheimer＇s dis- ease-like disease, but given its complexity it is not clear what specific aspect of enriched environ- ment has therapeutic effects. Studies from molecular biology have shown that the protein p300, which is a transcription co-activator required for consolidation of memories during specific learning tasks, is at the same time involved in DNA replication and repair, playing a central role in the long-patch pathway of base excision repair. Based on the evidence, we propose that learning tasks such as novel object recognition could be tested as possible methods of base excision repair fa- cilitation, hence inducing DNA repair in the hippocampal neurons. If this method proves to be effec- tive, it could be the start for designing similar tasks for humans, as a behavioral therapeutic com- plement to the classical drug-based therapy in treating neurodegenerative disorders.
Reactive oxygen species have been implicated in conditions ranging from cardiovascular dysfunc- tion, arthritis, cancer, to aging and age-related disorders. The organism developed several path- ways to counteract these effects, with base excision repair being responsible for repairing one of the major base lesions （8-oxoG） in all organisms. Epidemiological evidence suggests that cognitive stimulation makes the brain more resilient to damage or degeneration. Recent studies have linked enriched environment to reduction of oxidative stressin neurons of mice with Alzheimer＇s dis- ease-like disease, but given its complexity it is not clear what specific aspect of enriched environ- ment has therapeutic effects. Studies from molecular biology have shown that the protein p300, which is a transcription co-activator required for consolidation of memories during specific learning tasks, is at the same time involved in DNA replication and repair, playing a central role in the long-patch pathway of base excision repair. Based on the evidence, we propose that learning tasks such as novel object recognition could be tested as possible methods of base excision repair fa- cilitation, hence inducing DNA repair in the hippocampal neurons. If this method proves to be effec- tive, it could be the start for designing similar tasks for humans, as a behavioral therapeutic com- plement to the classical drug-based therapy in treating neurodegenerative disorders.
基金
supported by a grant from Synergon Consulting Company
a grant from Romanian Ministry for Education and Research,No.PCCE 140/2008
