The 100,000 Gbyte hard-drive we call our brain is a challenge to study, also making it a challenge to find therapeutic treatments against the numerous diseases that disrupt brain function. In my lab, slices of brain tissue are kept alive to examine neuronal connections responsible for both memory encoding and cellular maintenance pathways, and to study their vulnerability to pathogenesis. While the brain’s incredible density of synaptic connections allows for extraordinary memory capacity, the abundant synapses are also vulnerable to pathogenic over-activation. Such excitotoxic brain damage can occur in many disease states including stroke, traumatic injury, and seizure events. We are studying the pharmacological enhancement of endogenous pathways, and we found that positive modulation of internal repair mechanisms protects against the damaging effects of seizures and stroke-type excitotoxic insults. Other efforts are to study age-related neurodegenerative disorders. Every 72 seconds someone in the U.S. develops Alzheimer’s disease (AD). Reducing Alzheimer-type protein accumulation is essential for slowing the progression of the disease. Lysosomes and their degradative enzymes (e.g. cathepsins) are known to respond to AD, perhaps in an attempt to offset the abnormal protein accumulations that cause a distinct pathogenic cascade. Recently, we discovered a new class of drugs that act as positive modulators of the lysosomal response, resulting in the up-regulation of cathepsins as well as neuroprotection in cultured brain slices and in mouse models of AD.
Updated: Wednesday, January 5, 2011
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