دورية أكاديمية
أعرض في EDS

Selective inhibition of phosphodiesterase 4D increases tau phosphorylation at Ser214 residue.

التفاصيل البيبلوغرافية
العنوان: Selective inhibition of phosphodiesterase 4D increases tau phosphorylation at Ser214 residue.
المؤلفون: Villa V; Department of Experimental Medicine, Section of General Pathology, School of Medical and Pharmaceutical Sciences, University of Genoa, Genoa, Italy., Montalto G; Department of Experimental Medicine, Section of General Pathology, School of Medical and Pharmaceutical Sciences, University of Genoa, Genoa, Italy., Caudano F; Department of Experimental Medicine, Section of General Pathology, School of Medical and Pharmaceutical Sciences, University of Genoa, Genoa, Italy., Fedele E; Department of Pharmacy, Section of Pharmacology and Toxicology, School of Medical and Pharmaceutical Sciences, University of Genoa, Genoa, Italy.; IRCCS Ospedale Policlinico San Martino, Genoa, Italy., Ricciarelli R; Department of Experimental Medicine, Section of General Pathology, School of Medical and Pharmaceutical Sciences, University of Genoa, Genoa, Italy.; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
المصدر: BioFactors (Oxford, England) [Biofactors] 2022 Sep; Vol. 48 (5), pp. 1111-1117. Date of Electronic Publication: 2022 May 13.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Ios Press Country of Publication: Netherlands NLM ID: 8807441 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8081 (Electronic) Linking ISSN: 09516433 NLM ISO Abbreviation: Biofactors Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Ios Press
Original Publication: Oxford ; Washington, DC : Published for the International Union of Biochemistry by IRL Press, [c1988-
مواضيع طبية MeSH: Alzheimer Disease*/drug therapy , Alzheimer Disease*/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 4*/genetics , Cyclic Nucleotide Phosphodiesterases, Type 4*/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 4*/therapeutic use, Adenylyl Cyclases/metabolism ; Animals ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cyclic AMP-Dependent Protein Kinases/therapeutic use ; Phosphorylation ; Rats
مستخلص: Tau is a protein that normally participates in the assembly and stability of microtubules. However, it can form intraneuronal hyperphosphorylated aggregates that are hallmarks of Alzheimer's disease and other neurodegenerative disorders known as tauopathies. Tau can be phosphorylated by multiple kinases at several sites. Among such kinases, the cAMP-dependent protein kinase A (PKA) phosphorylates tau at Ser214 (pTAU-S214), an event that was shown to reduce the pathological assembly of the protein. Given that the neuronal cAMP/PKA-activated cascade is involved in synaptic plasticity and memory, and that cAMP-enhancing strategies demonstrated promising therapeutic potential for the treatment of cognitive deficits, we investigated the impact of cAMP on pTAU-S214 in N2a cells and rat hippocampal slices. Our results confirm that the activation of adenylyl cyclase increases pTAU-S214 in both model systems and, more interestingly, this effect is mimicked by GEBR-7b, a phosphodiesterase 4D inhibitor with proven pro-cognitive efficacy in rodents.
(© 2022 The Authors. BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)
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معلومات مُعتمدة: Università degli Studi di Genova
فهرسة مساهمة: Keywords: GEBR-7b; cyclic adenosine monophosphate; phosphodiesterase inhibitors; tau protein
المشرفين على المادة: EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4)
EC 4.6.1.1 (Adenylyl Cyclases)
تواريخ الأحداث: Date Created: 20220513 Date Completed: 20221018 Latest Revision: 20240910
رمز التحديث: 20240910
مُعرف محوري في PubMed: PMC9790528
DOI: 10.1002/biof.1847
PMID: 35561079
قاعدة البيانات: MEDLINE
الوصف
تدمد:1872-8081
DOI:10.1002/biof.1847