Exercise as Gene Therapy

Abstract

DNA damage is a common feature of neurodegenerative illnesses, and the ability to repair DNA strand breaks and lesions is crucial for neuronal survival (see Jeppesen et al1 and Shiwaku et al2 for reviews). Interventions aimed at repairing these lesions, therefore, could be useful for preventing or delaying the progression of disease. One potential strategy for promoting DNA damage repair (DDR) is exercise. Though the role of exercise in DDR is not understood, there is increasing evidence that simple physical activity may impact clinical outcomes for neurodegeneration. Here we discuss what is currently known about the molecular mechanisms of BDNF and how these mechanisms might influence the DDR process.

NMDA Receptor-Mediated Signaling Pathways Enhance Radiation Resistance, Survival and Migration in Glioblastoma Cells—A Potential Target for Adjuvant Radiotherapy

“…Interestingly, the mechanism of radiosensitization included a reduction of the proliferating cell nuclear antigen (PCNA), a protein involved in the repair of IR-induced DNA damage [51]. However, CREB-activity increases also the release of BDNF in neoplastic cells) [34,52]. Interestingly, BDNF is thought to contribute to DNA damage repair (overview in [52]) and promotes survival and migration in C6 glioma cells [53].…”

“…However, CREB-activity increases also the release of BDNF in neoplastic cells) [34,52]. Interestingly, BDNF is thought to contribute to DNA damage repair (overview in [52]) and promotes survival and migration in C6 glioma cells [53]. Furthermore, Yano and colleagues (1998) have demonstrated in neuroblastoma cells that Ca 2+ -entry through NMDAR phosphorylates a serine/threonine kinase Akt, which activates CREB and results in the release of a variety of anti-apoptotic signals facilitating cell survival [54].…”

Influence of Acute Exercise on DNA Repair and PARP Activity before and after Irradiation in Lymphocytes from Trained and Untrained Individuals

“…Moderate to high-intensity exercise can stimulate the adaptive responses by triggering endogenous antioxidant defense mechanisms against excessive ROS, thereby maintaining muscle redox balance [51] and enabling cells to cope with exposure to high levels of oxidants that would normally be toxic. Furthermore, emerging data identify regular physical exercise as one potential strategy for improving DNA repair capacity [9], thus enhancing the body’s capability to prevent and deal with diseases such as cancer. In order to enhance our understanding of the role of exercise in repairing DNA damage, we investigated the effect of acute exercise as well as aerobic fitness on the capacity of immune cells to repair radiation-induced DNA strand breaks and the role of PARP1 activity as a main player in initiating DNA repair.…”

“…At the molecular level, an acute bout of intense exercise induces transitory DNA damage, which is normally repaired within 24–72 h [8]. Several studies have specifically investigated the connection between exercise and DNA repair, suggesting an enhanced DNA repair through regular exercise [9] and a protective effect against radiation-induced DNA damage [10,11,12]. In the present study, we evaluated similar parameters in lymphocytes derived from trained versus untrained individuals.…”

Acquired Resilience: An Evolved System of Tissue Protection in Mammals

“…The observation that exercise mitigates the damage to DNA associated with age—telomere shortening and oxidative damage—has enjoyed considerable recent confirmation. 354–356 Correspondingly, one of the intriguing resilience responses of the heart—angina-induced protection against infarction—is lost in the elderly patients, except in a subcohort that exercised regularly. 273,274…”