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J Clin Invest. 2019 Oct 1;129(10):4539-4549. doi: 10.1172/JCI129987.

Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases.

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Institute of Hypoxia Medicine, Xuanwu Hospital and Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, and.
Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China.
Department of Internal Medicine and.
Departments of Pharmaceutical Care and Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Department of Pathology and Experimental Therapeutics, Bellvitge University Hospital-IDIBELL, Hospitalet de Llobregat and Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Center of Regenerative Medicine in Barcelona (CMRB) and Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Hospital Duran i Reynals, Hospitalet de Llobregat, Barcelona, Spain.
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
Departments of Internal Medicine and Epidemiology and.
Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China.
Howard Hughes Medical Institute, Departments of Internal Medicine, Neurology, and Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.


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.


Neuroscience; Parkinson’s disease

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