Journal article
Glycolysis-enhancing α 1 -adrenergic antagonists modify cognitive symptoms related to Parkinson's disease
NPJ Parkinson's Disease, Vol.9(1), 32
03/02/2023
DOI: 10.1038/s41531-023-00477-1
PMCID: PMC9981768
PMID: 36864060
Abstract
Terazosin is an α
-adrenergic receptor antagonist that enhances glycolysis and increases cellular ATP by binding to the enzyme phosphoglycerate kinase 1 (PGK1). Recent work has shown that terazosin is protective against motor dysfunction in rodent models of Parkinson's disease (PD) and is associated with slowed motor symptom progression in PD patients. However, PD is also characterized by profound cognitive symptoms. We tested the hypothesis that terazosin protects against cognitive symptoms associated with PD. We report two main results. First, in rodents with ventral tegmental area (VTA) dopamine depletion modeling aspects of PD-related cognitive dysfunction, we found that terazosin preserved cognitive function. Second, we found that after matching for demographics, comorbidities, and disease duration, PD patients newly started on terazosin, alfuzosin, or doxazosin had a lower hazard of being diagnosed with dementia compared to tamsulosin, an α
-adrenergic receptor antagonist that does not enhance glycolysis. Together, these findings suggest that in addition to slowing motor symptom progression, glycolysis-enhancing drugs protect against cognitive symptoms of PD.
Details
- Title: Subtitle
- Glycolysis-enhancing α 1 -adrenergic antagonists modify cognitive symptoms related to Parkinson's disease
- Creators
- Matthew A Weber - Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA. matthew-weber@uiowa.eduKartik Sivakumar - Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USAErvina E Tabakovic - Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USAMayu Oya - Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USAGeorgina M Aldridge - Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USAQiang Zhang - Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USAJacob E Simmering - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USANandakumar S Narayanan - Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- NPJ Parkinson's Disease, Vol.9(1), 32
- DOI
- 10.1038/s41531-023-00477-1
- PMID
- 36864060
- PMCID
- PMC9981768
- NLM abbreviation
- NPJ Parkinsons Dis
- ISSN
- 2373-8057
- eISSN
- 2373-8057
- Grant note
- NS120987 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) MH116043 / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- Language
- English
- Date published
- 03/02/2023
- Academic Unit
- Neurology; Pulmonary, Critical Care, and Occupational Medicine; Health Management and Policy; Iowa Neuroscience Institute; Pharmacy Practice and Science; Internal Medicine
- Record Identifier
- 9984375457602771
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