التفاصيل البيبلوغرافية
| العنوان: |
Extensive Anti-CoA Immunostaining in Alzheimer’s Disease and Covalent Modification of Tau by a Key Cellular Metabolite Coenzyme A |
| المؤلفون: |
Lashley, Tammaryn, Tossounian, Maria Armineh, Costello Heaven, Neve, Wallworth, Samantha, Peak-Chew, Sew, Bradshaw, Aaron, Cooper, J. Mark, de Silva, Rohan, Srai, Surjit Kaila, Malanchuk, Oksana, Filonenko, Valeriy, Koopman, Margreet B., Rüdiger, Stefan G.D., Skehel, Mark, Gout, Ivan |
| المساهمون: |
Sub Cellular Protein Chemistry, Cellular Protein Chemistry |
| سنة النشر: |
2021 |
| مصطلحات موضوعية: |
Alzheimer’s disease, Coenzyme A, neurodegeneration, oxidative stress, protein CoAlation, tau, Cellular and Molecular Neuroscience |
| الوصف: |
Alzheimer’s disease (AD) is a neurodegenerative disorder, accounting for at least two-thirds of dementia cases. A combination of genetic, epigenetic and environmental triggers is widely accepted to be responsible for the onset and development of AD. Accumulating evidence shows that oxidative stress and dysregulation of energy metabolism play an important role in AD pathogenesis, leading to neuronal dysfunction and death. Redox-induced protein modifications have been reported in the brain of AD patients, indicating excessive oxidative damage. Coenzyme A (CoA) is essential for diverse metabolic pathways, regulation of gene expression and biosynthesis of neurotransmitters. Dysregulation of CoA biosynthesis in animal models and inborn mutations in human genes involved in the CoA biosynthetic pathway have been associated with neurodegeneration. Recent studies have uncovered the antioxidant function of CoA, involving covalent protein modification by this cofactor (CoAlation) in cellular response to oxidative or metabolic stress. Protein CoAlation has been shown to both modulate the activity of modified proteins and protect cysteine residues from irreversible overoxidation. In this study, immunohistochemistry analysis with highly specific anti-CoA monoclonal antibody was used to reveal protein CoAlation across numerous neurodegenerative diseases, which appeared particularly frequent in AD. Furthermore, protein CoAlation consistently co-localized with tau-positive neurofibrillary tangles, underpinning one of the key pathological hallmarks of AD. Double immunihistochemical staining with tau and CoA antibodies in AD brain tissue revealed co-localization of the two immunoreactive signals. Further, recombinant 2N3R and 2N4R tau isoforms were found to be CoAlated in vitro and the site of CoAlation mapped by mass spectrometry to conserved cysteine 322, located in the microtubule binding region. We also report the reversible H2O2-induced dimerization of recombinant 2N3R, which is inhibited by CoAlation. Moreover, CoAlation of ... |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| تدمد: |
1662-5102 |
| العلاقة: |
https://dspace.library.uu.nl/handle/1874/413887Test |
| الإتاحة: |
https://dspace.library.uu.nl/handle/1874/413887Test |
| حقوق: |
info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: |
edsbas.4E32A42F |
| قاعدة البيانات: |
BASE |
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