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© 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Introduction

The discovery of biogenic aldehydes in the postmortem parkinsonian brain and the ability of these aldehydes to modify and cross-link proteins has called attention to their possible role in Parkinson's disease. For example, many in vitro studies have found that the aldehyde metabolite of dopamine, 3,4-dihydroxyphenylacetaldehyde (DOPAL), induces the formation of stable, neurotoxic alpha-synuclein oligomers.

Methods

To study this in vivo, mice deficient in the two aldehyde dehydrogenase enzymes (Aldh1a1 and Aldh2, DKO) primarily responsible for detoxification of DOPAL in the nigrostriatal pathway were crossed with mice that overexpress human wild-type alpha-synuclein. DKO overexpressing human wild-type alpha-synuclein (DKO/ASO) offspring were evaluated for impairment on motor tasks associated with Parkinsonism.

Results

DKO/ASO mice developed severe motor deficits greater than that of mice overexpressing human wild-type alpha-synuclein alone.

Conclusion

These results provide evidence to support the idea that biogenic aldehydes such as DOPAL interact with human wild-type alpha-synuclein, directly or indirectly, in vivo to exacerbate locomotor deficits in Parkinson's disease.

Details

Title
Impaired aldehyde detoxification exacerbates motor deficits in an alpha-synuclein mouse model of Parkinson's disease
Author
Martinez, Paul Anthony 1   VIAFID ORCID Logo  ; Vanessa Elia Martinez 2 ; Rani, Sheela 3 ; Murrell, Meredith 4 ; Javors, Martin 5 ; Gelfond, Jonathan 6 ; Doorn, Jonathan Alan 7 ; Fernandez, Elizabeth 8 ; Strong, Randy 9 

 Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas, USA; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas, USA; Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas, USA 
 Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas, USA 
 Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas, USA; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas, USA 
 Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA 
 Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas, USA; Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA 
 Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA; Department of Epidemiology & Biostatistics, University of Texas Health Science Center, San Antonio, Texas, USA 
 Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa, USA 
 Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas, USA; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas, USA; Geriatric Research, Education, and Clinical Center, South Texas Veterans Health. Care Network, San Antonio, Texas, USA 
 Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas, USA; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas, USA; Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas, USA; Geriatric Research, Education, and Clinical Center, South Texas Veterans Health. Care Network, San Antonio, Texas, USA 
Section
ORIGINAL ARTICLES
Publication year
2023
Publication date
Sep 2023
Publisher
John Wiley & Sons, Inc.
e-ISSN
21623279
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2864049546
Copyright
© 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.