Research

Apoptosis in a dopamine neuron The major goal of our laboratory is to identify the processes underlying the degeneration of neurons in Parkinson’s disease and related disorders. Parkinson’s disease is characterized by impaired motor control, including tremor, rigidity and slowness of movement. These disturbances are due to the loss of dopamine neurons of the substantia nigra of the midbrain. One of the current major hypotheses of this neuron loss is that it is due to programmed cell death (also known as apoptosis), a form of death in which genes intrinsic to the cell bring about its own destruction.

..Programmed Cell Death in Dopamine Neurons
We have shown that apoptosis occurs during the normal development of dopamine neurons [Mol Cell Neurosci ‘93], and that it can be regulated by target interaction [PNAS ‘94]. We have also shown that apoptosis can be induced in dopamine neurons in models of parkinsonism [J Neurosci ‘97]. Therefore, one of our principal goals is to better define the molecular basis of apoptosis in dopamine neurons. We have a particular interest in identifying upstream mediators which may serve as therapeutic targets. An example of such is the MAPK signaling cascade, mediating phosphorylation of c-jun in models of apoptosis of dopamine neurons [J Neurochem '99].

..Neurotrophic Factors for Dopamine Neurons
During development, the number of neurons which die due to apoptosis is regulated by the availability of protein neurotrophic factors. We have shown that glial cell line-derived neurotrophic factor (GDNF) may be such a factor for developing dopamine neurons [J Neurochem ’98; J Neurosci 2003]. Therefore, another of our research goals is to define the role of GDNF, and its mechanisms in supporting the viability of these neurons.