Parkinson disease (PD) is a devastating neurodegenerative disease characterized by a distinct set of motor symptoms. Although the etiology of PD remains poorly understood, the familial form of PD is influenced by genetic mutations. Recently, several genetic loci have been implicated in the pathogenesis of familial PD. Although the loci of these genes are different, there are sufficient similarities in the phenotypes of their patients, which strongly implicated the functional links of these diverse target proteins. My laboratory has long-standing interests to study the pathogenesis of Parkinson disease, especially focusing on genetics aspect.
In addition to PD, the abnormal protein aggregation is commonly observed in many neurodegenerative diseases, such as Alzheimer and Huntington diseases, and thought to play a critical role in the pathogenesis of these diverse brain defects. In another project we are exploring the effects on the various modes of protein modification and its subsequent protein aggregation on neuronal death and the pathogenesis of neurodegenerative disorders. In addition, by focusing on the several target proteins, we are trying to examine and develop many possible tools to modulate the protein aggregation, through target- modification, degradation, and cross-linking. Those studies would be expected to provide a useful basis for the future development of more efficient therapeutic methods and drug targets for many neurodegenerative diseases.
Down syndrome (DS) is the most common genetic disorder, characterized by mental retardation, congenital heart abnormalities, and susceptibility to Alzheimer disease. Brain development of DS patients is associated with elevated apoptosis and abnormal neuronal differentiation. Those key features are closely associated with many genes mapped within Down syndrome critical region (DSCR) on human chromosome 21. Another main ongoing project in the lab is to study the functional role of DS target genes within DSCR and the pathogenesis of DS neural defects.