Parkinson's disease (PD) is a common neurodegenerative disease that lacks therapies to prevent progressive neurodegeneration. Impaired energy metabolism and reduced ATP levels are common features of PD. Previous studies revealed that terazosin (TZ) enhances the activity of phosphoglycerate kinase 1 (PGK1), thereby stimulating glycolysis and increasing cellular ATP levels. Therefore, we asked whether enhancement of PGK1 activity would change the course of PD. In toxin-induced and genetic PD models in mice, rats, flies, and induced pluripotent stem cells, TZ increased brain ATP levels and slowed or prevented neuron loss. The drug increased dopamine levels and partially restored motor function. Because TZ is prescribed clinically, we also interrogated 2 distinct human databases. We found slower disease progression, decreased PD-related complications, and a reduced frequency of PD diagnoses in individuals taking TZ and related drugs. These findings suggest that enhancing PGK1 activity and increasing glycolysis may slow neurodegeneration in PD.

No abstract

Background and Purpose-There is evidence and international consensus on the advantages and potential of a polypill for established cardiovascular disease patients to improve adherence in the secondary prevention of cardiovascular disease. This study aimed to estimate the numbers of stroke patients who would be eligible for the polypill strategy in China, and the suitable composition of a polypill, based on data of the China National Stroke Prevention Project. Methods-A total of 717 620 residents aged ≥40 years from 6 Chinese representative provinces were screened for prevalent stroke from 2011 to 2012 with an 84.4% response rate. Participants with a history of stroke received further investigation of risk factors and treatments. The potential need for treatment was classified according to the guidelines. Rates were standardized using the population composition of the Sixth National Population Census of China. Results-The standardized prevalence rate of stroke was 1.9%. Up to 93.1% of stroke patients were eligible for a polypill containing at least 2 types of medications, with 75.3% eligible for a statin and antiplatelet agent and 70.6% for antihypertensive and antiplatelet medications. Considering 3 therapies, 54% were eligible for antihypertensive, statin, and antiplatelet medications. The current treatment rate with all required combinations of separate pills was only 6.9%. Conclusions-A huge number of stroke patients in China require preventive therapy and would be eligible for a polypill.This study indicates that it would be reasonable to consider and assess the value of a polypill strategy to improve secondary prevention of stroke in China.

Circadian biology modulates almost all aspects of mammalian physiology, disease, and response to therapies. Emerging data suggest that circadian biology may significantly affect the mechanisms of susceptibility, injury, recovery, and the response to therapy in stroke. In this review/perspective, we survey the accumulating literature and attempt to connect molecular, cellular, and physiological pathways in circadian biology to clinical consequences in stroke. Accounting for the complex and multifactorial effects of circadian rhythm may improve translational opportunities for stroke diagnostics and therapeutics.