PGC1-α

PGC-1α plays an essential role in protecting against oxidative stress in the brain and regulating mitochondrial antioxidant genes. In the lab, we use stereotaxic techniques in mice to overexpress PGC-1α in the substantia nigra and examine whether it will protect against MPTP toxicity and the chronic degeneration that occurs in transgenic mice overexpressing alpha-synuclein (αSyn). Our initial studies demonstrate a surprising downregulation of Pitx3, a transcription factor significantly involved in the maintenance and survival of dopaminergic neurons when PGC-1α is overexpressed at high levels. We are now investigating strategies to achieve the neuroprotective potential of PGC-1α as a therapeutic target while avoiding this potentially harmful effect on Pitx3.