We study the cellular and molecular mechanisms underlying neurodegeneration in Drosophila and mouse neurodegenerative models with the combination of electrophysiology, morphology, genetics, molecular biology, biochemistry and behavior techniques.
Alzheimer's disease (AD), characterized by a progressive loss of learning and memory, accounts for one half (or more) of dementia cases in the elderly people. A major consensus in current AD study is that cognitive deficits in AD, at least in early stages, are due to synaptic dysfunction and synapse loss, and that accumulation of beta amyloid (AŽ┬), oligomeric forms in particular, plays a causal and central role in AD. However, the nature and progression of synaptic changes in AD and the underlying molecular mechanisms are essentially unknown.
In the last several years, we generated a neural circuit AD model by expressing AŽ┬ in adult flies with a tissue specific driver. With the model, we perform extensive time-course analysis of age-dependent structural and functional changes in the soma, axon and presynaptic terminals of identified single neurons, and study the cellular and molecular mechanisms of these changes. We also use this model to conduct genetic screening for modifiers of age-dependent neuron injuries induced by expression of AŽ┬. Moreover, to gain a closer insight into the neurodegeneration in patients, we test our findings on APP/Presenilin mice.
- The nature and progression of age-dependent structural and functional changes in the soma, axon and presynaptic terminals of identified single neurons induced by expression of AŽ┬ in Drosophila.
- The roles of potential mediators/regulators in neuron injuries induced by AŽ┬ expression.
- Genetic screening for modifiers of age-dependent neuron injuries induced by AŽ┬ expression.
- Genetic screening for fly mutants with increased resistance to hypoxia.