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Cited by 286Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeurological disorders and treatments

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

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Cai, Rong, Zhang, Yu, Simmering, Jacob E., Schultz, Jordan L., Li, Yuhong, Fernandez-Carasa, Irene, Consiglio, Antonella, Raya, Angel +11 more·2019·Journal of Clinical Investigation
DOI 10.1172/jci129987PMC PMC6763248
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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.

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Authors
Cai, R., Zhang, Y., Simmering, J. E., Schultz, J. L., Li, Y., Fernandez-Carasa, I., Consiglio, A., Raya, A., Polgreen, P. M., Narayanan, N. S., Yuan, Y., Chen, Z., Su, W., Han, Y., Zhao, C., Gao, L., Ji, X., Welsh, M. J., & Liu, L.
Affiliations
  • Capital Medical University (CN)
  • University of Iowa (US)
  • Bellvitge University Hospital (ES)
  • Beihang University (CN)
Corresponding author
  • Welsh, Michael J.
  • Liu, Lei
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2019-09-16
Volume
129
Issue
10
Pages
4539-4549
ISSN
  • 0021-9738 (ISSN-L)
  • 1558-8238
DOI
10.1172/jci129987
PMC
PMC6763248
OpenAlex
W2973064436
Cited by
286
References
2
Citations by year
2026: 37 · 2025: 57 · 2024: 51 · 2023: 48 · 2022: 35 · 2021: 33 · 2020: 21 · 2019: 4
FWCI
15.55
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
Funders
  • National Natural Science Foundation of China (NSFC 91649201, 31771121)
  • Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201706)
  • Spanish Ministry of Economy and Competitiveness (SAF2015-69706-R to AR, BFU2016-80870-P)
  • Instituto de Salud Carlos III- ISCIII/FEDER (Red de Terapia Celular - TerCel RD16/0011/0024, PIE14/00061)
  • European Research Council (2012-StG (311736- PD-HUMMODEL),and,(2017-SGR-899))
  • CERCA Programme/Generalitat de Catalunya (N/A)
  • Howard Hughes Medical Institute (N/A)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
Keywords
Parkinson's disease, glycolysis, PGK1, terazosin, ATP levels, energy metabolism, neurodegeneration, dopamine, motor function, induced pluripotent stem cells, drug repurposing
MeSH terms
Adenosine Triphosphate, Aged, Aged, 80 and over, Animals, Brain, Dopamine, Drosophila melanogaster, Female, Glycolysis, Humans, Male, Mice, Inbred C57BL, Nerve Degeneration, Parkinson Disease, Phosphoglycerate Kinase, Prazosin, Disease Progression, Parkinsonian Disorders, Mice, Rats, Induced Pluripotent Stem Cells

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