Journal article
Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases
The Journal of clinical investigation, Vol.129(10), pp.4539-4549
10/01/2019
DOI: 10.1172/JCI129987
PMCID: PMC6763248
PMID: 31524631
Abstract
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.
Details
- Title: Subtitle
- Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases
- Creators
- Rong Cai - Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, ChinaYu Zhang - State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, ChinaJacob E Simmering - Department of Internal Medicine andJordan L Schultz - Departments of Pharmaceutical Care and Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAYuhong Li - Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, ChinaIrene Fernandez-Carasa - Department of Pathology and Experimental Therapeutics, Bellvitge University Hospital-IDIBELL, Hospitalet de Llobregat and Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, SpainAntonella Consiglio - Department of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyAngel Raya - Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, SpainPhilip M Polgreen - Departments of Internal Medicine and Epidemiology andNandakumar S Narayanan - Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAYanpeng Yuan - Institute of Hypoxia Medicine, Xuanwu Hospital and Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, andZhiguo Chen - Institute of Hypoxia Medicine, Xuanwu Hospital and Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, andWenting Su - Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, ChinaYanping Han - Institute of Hypoxia Medicine, Xuanwu Hospital and Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, andChunyue Zhao - Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, ChinaLifang Gao - Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, ChinaXunming Ji - Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, ChinaMichael J Welsh - Howard Hughes Medical Institute, Departments of Internal Medicine, Neurology, and Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USALei Liu - Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.129(10), pp.4539-4549
- DOI
- 10.1172/JCI129987
- PMID
- 31524631
- PMCID
- PMC6763248
- NLM abbreviation
- J Clin Invest
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Publisher
- United States
- Grant note
- P01 HL091842 / NHLBI NIH HHS UL1 TR002537 / NCATS NIH HHS
- Language
- English
- Date published
- 10/01/2019
- Academic Unit
- Neurology; Psychiatry; Infectious Diseases; Health Management and Policy; Pharmacy Practice and Science; Injury Prevention Research Center; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Epidemiology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984070514602771
Metrics
30 Record Views