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Pharmacomimetics of Exercise: Novel Approaches for Hippocampally- Targeted Neuroprotective Agents

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Coordinated and constructive physical activity is correlated with the maintenance of cognitive function in humans. Voluntary running also enhances neuroplasticity in adult and aging rodents, but the molecular pathways underlying these effects are still being elucidated. Considering the multifactorial nature of the biochemical links between physical activity and neurophysiology, it is likely that there are many pharmacological mechanisms by which the beneficial actions of exercise can be effectively reproduced using chemical agents. Most studies to date have focused on brain-derived neurotrophic factor (BDNF) as a signaling target for the enhancement of neuronal function by exercise. The goal of the current review is to move beyond BDNF by exploring the diversity of molecular pathways regulated by physical activity in a variety of situations. We will discuss the availability and mechanism of action for several diverse physical activity pharmacomimetics. As physical activity enhances both neuroplasticity and cognition, understanding the molecular targets for these effects may lead to the development of potent new therapeutic interventions for age-related neurodegenerative conditions such as Alzheimer's disease.

Keywords: Running; Wnt; exercise; hippocampus; insulin-like growth factor; neurogenesis; nitric oxide; serotonin

Document Type: Research Article


Affiliations: National Institute on Aging, Biomedical Research Center, Suite 100, Room 5C228, 251 Bayview Boulevard, Baltimore MD 21224, USA.

Publication date: December 1, 2009

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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