Use of Okadaic Acid to Identify Relevant Phosphoepitopes in Pathology: A Focus on Neurodegeneration
Protein phosphorylation is involved in the regulation of a wide variety of physiological processes and is the result of a balance between protein kinase and phosphatase activities. Biologically active marine derived compounds have been shown to represent an interesting source of novel compounds that...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2013-05-01
|
| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1660-3397/11/5/1656 |
| _version_ | 1828365344492748800 |
|---|---|
| author | Jesús Avila Miguel Medina Nieves Villanueva |
| author_facet | Jesús Avila Miguel Medina Nieves Villanueva |
| author_sort | Jesús Avila |
| collection | DOAJ |
| description | Protein phosphorylation is involved in the regulation of a wide variety of physiological processes and is the result of a balance between protein kinase and phosphatase activities. Biologically active marine derived compounds have been shown to represent an interesting source of novel compounds that could modify that balance. Among them, the marine toxin and tumor promoter, okadaic acid (OA), has been shown as an inhibitor of two of the main cytosolic, broad-specificity protein phosphatases, PP1 and PP2A, thus providing an excellent cell-permeable probe for examining the role of protein phosphorylation, and PP1 and PP2A in particular, in any physiological or pathological process. In the present work, we review the use of okadaic acid to identify specific phosphoepitopes mainly in proteins relevant for neurodegeneration. We will specifically highlight those cases of highly dynamic phosphorylation-dephosphorylation events and the ability of OA to block the high turnover phosphorylation, thus allowing the detection of modified residues that could be otherwise difficult to identify. Finally, its effect on tau hyperhosphorylation and its relevance in neurodegenerative pathologies such as Alzheimer’s disease and related dementia will be discussed. |
| first_indexed | 2024-04-14T05:28:49Z |
| format | Article |
| id | doaj.art-00fe4a907a4e40fa9da9928c4b434aa4 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-14T05:28:49Z |
| publishDate | 2013-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-00fe4a907a4e40fa9da9928c4b434aa42022-12-22T02:09:52ZengMDPI AGMarine Drugs1660-33972013-05-011151656166810.3390/md11051656Use of Okadaic Acid to Identify Relevant Phosphoepitopes in Pathology: A Focus on NeurodegenerationJesús AvilaMiguel MedinaNieves VillanuevaProtein phosphorylation is involved in the regulation of a wide variety of physiological processes and is the result of a balance between protein kinase and phosphatase activities. Biologically active marine derived compounds have been shown to represent an interesting source of novel compounds that could modify that balance. Among them, the marine toxin and tumor promoter, okadaic acid (OA), has been shown as an inhibitor of two of the main cytosolic, broad-specificity protein phosphatases, PP1 and PP2A, thus providing an excellent cell-permeable probe for examining the role of protein phosphorylation, and PP1 and PP2A in particular, in any physiological or pathological process. In the present work, we review the use of okadaic acid to identify specific phosphoepitopes mainly in proteins relevant for neurodegeneration. We will specifically highlight those cases of highly dynamic phosphorylation-dephosphorylation events and the ability of OA to block the high turnover phosphorylation, thus allowing the detection of modified residues that could be otherwise difficult to identify. Finally, its effect on tau hyperhosphorylation and its relevance in neurodegenerative pathologies such as Alzheimer’s disease and related dementia will be discussed.http://www.mdpi.com/1660-3397/11/5/1656AlzheimerGSK-3kinasesneurodegenerationokadaic acidphosphatasesphosphorylationPP2Atanglestau |
| spellingShingle | Jesús Avila Miguel Medina Nieves Villanueva Use of Okadaic Acid to Identify Relevant Phosphoepitopes in Pathology: A Focus on Neurodegeneration Marine Drugs Alzheimer GSK-3 kinases neurodegeneration okadaic acid phosphatases phosphorylation PP2A tangles tau |
| title | Use of Okadaic Acid to Identify Relevant Phosphoepitopes in Pathology: A Focus on Neurodegeneration |
| title_full | Use of Okadaic Acid to Identify Relevant Phosphoepitopes in Pathology: A Focus on Neurodegeneration |
| title_fullStr | Use of Okadaic Acid to Identify Relevant Phosphoepitopes in Pathology: A Focus on Neurodegeneration |
| title_full_unstemmed | Use of Okadaic Acid to Identify Relevant Phosphoepitopes in Pathology: A Focus on Neurodegeneration |
| title_short | Use of Okadaic Acid to Identify Relevant Phosphoepitopes in Pathology: A Focus on Neurodegeneration |
| title_sort | use of okadaic acid to identify relevant phosphoepitopes in pathology a focus on neurodegeneration |
| topic | Alzheimer GSK-3 kinases neurodegeneration okadaic acid phosphatases phosphorylation PP2A tangles tau |
| url | http://www.mdpi.com/1660-3397/11/5/1656 |
| work_keys_str_mv | AT jesusavila useofokadaicacidtoidentifyrelevantphosphoepitopesinpathologyafocusonneurodegeneration AT miguelmedina useofokadaicacidtoidentifyrelevantphosphoepitopesinpathologyafocusonneurodegeneration AT nievesvillanueva useofokadaicacidtoidentifyrelevantphosphoepitopesinpathologyafocusonneurodegeneration |