Models of AD being employed include transgenic mice which have been engineered to express mutant genes known cause early-onset inherited AD, models of PD include. Perhaps of equal importance to knowledge of the molecular and cellular mechanisms that result in neuronal dysfunction and death in age-related neurodegenerative disorders, is a better understanding of successful brain aging at the cellular and molecular levels. A major goal of research in the laboratory is to identify the cellular signaling mechanisms that promote the survival and plasticity of neurons during aging. They have shown that signaling pathways activated by neurotrophic factors and certain cytokines can increase resistance of neurons to degeneration in experimental models of neurodegenerative disorders. The specific molecular and biochemical changes that participate in such beneficial signaling mechanisms are currently under study.
Synapses are sites of where neurotransmission and trophic factor signaling occurs.
Synaptic signaling pathways play fundamental roles in both immediate brain functions such as visual recognition and responses, and body movements, and long-term changes such as learning and memory. Recent findings suggest that alterations in synaptic signaling occur very early in the course of AD and other age-related neurodegenerative disorders. The impact of oxidative stress, neurotrophic factor and cytokine signaling, and genetic aberrancies on synaptic physiology are being examined. Work is currently focussing on synaptic physiology, molecular biology and biochemistry in experimental animal models of neurodegenerative disorders. Interestingly, DR increases neurogenesis in the hippocampus which may possibly contribute to enhanced cognitive function and resistance to injury.