|PGC-1α’s Emerging Roles—Neuroprotection and Neurodegeneration
Four recent articles focus on the importance of the peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), a transcriptional regulator involved in mitochondrial biogenesis, tissue differentiation, and energy homeostasis. One paper illustrates the protein’s neuroprotective role while three implicate its loss of function as a cause of neurodegeneration. St-Pierre and colleagues (1) show that PGC-1α transcription is upregulated in response to reactive oxygen species (ROS). Consequently, this increase in PGC-1α leads to higher expression of genes that are involved in suppressing ROS toxicity. In addition, their study showed that ablation of PGC-1α increased susceptibility to neuronal insults induced by ROS-generating toxins and depolarizing agents. In contrast, PGC-1α overexpression protected against ROS insults, further cementing the important role this protein plays in neuroprotection.
The other studies present evidence that decreased expression and/or loss of function of PGC-1α underlie...