Tae-In Kam 00:00:05
Hi, my name is Tae-In Kam from Johns Hopkins University. I'm an assistant professor in the Department of Neurology.
My research is related to the molecular mechanisms of Parkinson's disease induced by the alpha-synuclein protein, the main cause of Parkinson's disease. While pathological accumulation of aggregated alpha-synuclein protein is a main cause of Parkinson's disease, how this aggregated alpha-synuclein protein causes neurodegeneration is largely unknown. We originally found that alpha-synuclein protein induces neural cell death in a PARP-1-dependent manner, which means that targeting PARP-1 inhibition could be a new therapeutic target for Parkinson's disease.
With research support from the Parkinson's Foundation, I propose to identify the two novel regulators of the PARP-1 enzyme. One is the upstream regulator that regulates the activity of PARP-1, and the other is the downstream regulator that is activated and actually causes neural cell death after PARP-1 activation. From our research, we will provide new, multifaceted therapeutic targets against neural cell death in Parkinson's disease.
Tae-In Kam 00:01:25
Let's go back to our original paper, which was published in Science in 2018. PARP-1 is an enzyme that is activated during the DNA damage response under normal conditions. We first identified that alpha-synuclein aggregates caused hyperactivation of PARP-1 in response to the high accumulation of DNA damage stress. Interestingly, PARP-1 inhibition showed drastic reductions of parkinsonism pathologies, including neuronal cell death, decreased dopamine levels and movement behavior deficits, which means inhibiting PARP-1 is critical for Parkinson's pathogenesis.
I think the most hopeful aspect for my work with Parkinson's disease is the potential for positive impacts on the disease. The progress brings hope for improved treatments or some quality of life for those who are affected by Parkinson's disease.
The Parkinson's Foundation provides critical support for my laboratory efforts to tackle the big questions in Parkinson's disease: what is the fundamental molecular mechanism of Parkinson's disease? Your support provides a critical catalyst for developing my research program to pursue interesting and quite innovative research. With the help of your support, I will take a big step to be a leader in this field.