Cai, R et al. J. Clin. Invest. 129, 4539─4549 (2019)

Parkinson’s disease (PD) is a common neurodegenerative disease with no cure. Several mechanisms, including metabolic dysfunction, have been proposed to contribute to neuron death in PD. The observation that energy deficits and reduced ATP levels are common features of PD led investigators to hypothesize that increasing glycolysis might be a therapeutic option to slow the neurodegeneration associated with PD. They administered terazosin (TZ) a drug that binds and activates phosphoglycerate kinase 1 (PGK1) — the first ATP-generating enzyme in glycolysis — to genetic and toxin-induced PD models in mice, rats and flies, and showed that TZ increased brain ATP levels and slowed neuron loss. These findings suggest that PGK1 and glycolysis could be targeted to slow PD progression.