Profiles of brain oxidative damage, ventricular alterations, and neurochemical metabolites in the striatum of PINK1 knockout rats as functions of age and gender: Relevance to Parkinson disease
Open accessAbstract
Parkinson disease (PD) is the second most common neurodegenerative disease associated with aging. Dopaminergic neuronal degeneration and α-synuclein aggregation are commonly found in PD brain. Oxidative damage and inflammation often are considered as etiological factors of PD, although the detailed mechanisms still remain unknown. Gender and aging are two important risk factors to PD, and gene mutations and certain environmental factors have been implicated in this disease. The current study employed PTEN-induced putative kinase -1 (PINK1) knockout (KO) rats, since mutations in PINK-1 lead to familial PD. We evaluated the oxidative damage in the brain of PINK1 KO rats, and we used MRI and MRS to measure the ventricle sizes and neurochemical metabolite profiles in these rats as a function of age and gender. Distinct gender- and age-related alterations were found. The results are discussed with respect to the suitabililty of this unique rat as a faithful model of known characteristics of PD.
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Hydroxyl radical reaction with proteins leads to incorporation of carbonyl functionalities and alterations in protein conformation, normally with loss of function.
“The former leads to the incorporation of carbonyl functionalities in proteins and alterations in protein conformation (and normally loss of function as a consequence) [8,22,23,24]”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [24]
The Methods (Slot blot assay; page unavailable) measure protein carbonyls, and the Discussion (page unavailable) treats them as biomarkers of oxidative damage. The paper does not say that hydroxyl radicals incorporate carbonyl groups into proteins or that this changes protein conformation and normally causes loss of function. (LLM, conf=0.82)
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- Authors
- Ren, X., Hinchie, A., Swomley, A., Powell, D. K., & Butterfield, D. A.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Butterfield, D. Allan
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 143
- Pages
- 146-152
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC6848777
- OpenAlex
- W2967373776
- Cited by
- 29
- References
- 34
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 13 · 2020: 6 · 2019: 1
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1R21NS094891)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- Parkinson's disease, oxidative damage, ventriculomegaly, striatum, aging, sex differences, familial Parkinson's disease, magnetic resonance imaging, magnetic resonance spectroscopy, dopaminergic neurons, alpha-synuclein aggregation, neuroinflammation
- MeSH terms
- PTEN-Induced Putative Kinase, Animals, Aspartic Acid, Brain, Corpus Striatum, Disease Models, Animal, Female, Glutamine, Glutathione, Inositol, Magnetic Resonance Imaging, Male, Magnetic Resonance Spectroscopy, Parkinson Disease, Protein Kinases, Taurine, Biomarkers, Oxidative Stress, Neurodegenerative Diseases, Rats, Gene Knockout Techniques
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