Modulation of neuronal survival factor MEF2 by kinases in Parkinson’s disease
Parkinson’s disease (PD) is the second most common neurodegenerative disorder due to selective death of neurons in the substantia nigra pars compacta (SNpc). The cause of cell death remains largely unknown. Myocyte enhancer factor 2 (MEF2) is a group of transcriptional factors required to regulate n...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-05-01
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| Series: | Frontiers in Physiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00171/full |
| _version_ | 1818505731628859392 |
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| author | Yue eYin Yue eYin Hua eShe Wenming eLi Qian eYang Shuzhong eGuo Zixu eMao |
| author_facet | Yue eYin Yue eYin Hua eShe Wenming eLi Qian eYang Shuzhong eGuo Zixu eMao |
| author_sort | Yue eYin |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is the second most common neurodegenerative disorder due to selective death of neurons in the substantia nigra pars compacta (SNpc). The cause of cell death remains largely unknown. Myocyte enhancer factor 2 (MEF2) is a group of transcriptional factors required to regulate neuronal development, synaptic plasticity, as well as survival. Recent studies show that MEF2 functions are regulated in multiple subcellular organelles and suggest that dysregulation of MEF2 plays essential roles in the pathogenesis of PD. Many kinases associated with transcription, translation, protein misfolding, autophagy, and cellular energy homeostasis are involved in the neurodegenerative process. Following the first demonstration that mitogen-activated protein kinase p38 (p38 MAPK) directly phosphorylates and activates MEF2 to promote neuronal survival, several other kinase regulators of MEF2s have been identified. These include protein kinase A (PKA) and extracellular signal regulated kinase 5 (ERK5) as positive MEF2 regulators, and cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase 3β (GSK3β) as negative regulators in response to diverse toxic signals relevant to PD. It is clear that MEF2 has emerged as a key point where survival and death signals converge to exert their regulatory effects, and dysregulation of MEF2 function in multiple subcellular organelles may underlie PD pathogenesis. Moreover, several other kinases such as leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced putative kinase 1 (PINK1) are of particular interest due to their potential interaction with MEF2. |
| first_indexed | 2024-12-10T21:54:56Z |
| format | Article |
| id | doaj.art-9f14bf1e53b44c4dad49a1dcceb41548 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-10T21:54:56Z |
| publishDate | 2012-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-9f14bf1e53b44c4dad49a1dcceb415482022-12-22T01:32:04ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2012-05-01310.3389/fphys.2012.0017127091Modulation of neuronal survival factor MEF2 by kinases in Parkinson’s diseaseYue eYin0Yue eYin1Hua eShe2Wenming eLi3Qian eYang4Shuzhong eGuo5Zixu eMao6Fourth Military Medical UniversityEmory UniversityEmory UniversityEmory UniversityEmory UniversityFourth Military Medical UniversityEmory UniversityParkinson’s disease (PD) is the second most common neurodegenerative disorder due to selective death of neurons in the substantia nigra pars compacta (SNpc). The cause of cell death remains largely unknown. Myocyte enhancer factor 2 (MEF2) is a group of transcriptional factors required to regulate neuronal development, synaptic plasticity, as well as survival. Recent studies show that MEF2 functions are regulated in multiple subcellular organelles and suggest that dysregulation of MEF2 plays essential roles in the pathogenesis of PD. Many kinases associated with transcription, translation, protein misfolding, autophagy, and cellular energy homeostasis are involved in the neurodegenerative process. Following the first demonstration that mitogen-activated protein kinase p38 (p38 MAPK) directly phosphorylates and activates MEF2 to promote neuronal survival, several other kinase regulators of MEF2s have been identified. These include protein kinase A (PKA) and extracellular signal regulated kinase 5 (ERK5) as positive MEF2 regulators, and cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase 3β (GSK3β) as negative regulators in response to diverse toxic signals relevant to PD. It is clear that MEF2 has emerged as a key point where survival and death signals converge to exert their regulatory effects, and dysregulation of MEF2 function in multiple subcellular organelles may underlie PD pathogenesis. Moreover, several other kinases such as leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced putative kinase 1 (PINK1) are of particular interest due to their potential interaction with MEF2.http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00171/fullAutophagyMitochondriaParkinson's diseaseneurodegenerationkinaseMEF2 |
| spellingShingle | Yue eYin Yue eYin Hua eShe Wenming eLi Qian eYang Shuzhong eGuo Zixu eMao Modulation of neuronal survival factor MEF2 by kinases in Parkinson’s disease Frontiers in Physiology Autophagy Mitochondria Parkinson's disease neurodegeneration kinase MEF2 |
| title | Modulation of neuronal survival factor MEF2 by kinases in Parkinson’s disease |
| title_full | Modulation of neuronal survival factor MEF2 by kinases in Parkinson’s disease |
| title_fullStr | Modulation of neuronal survival factor MEF2 by kinases in Parkinson’s disease |
| title_full_unstemmed | Modulation of neuronal survival factor MEF2 by kinases in Parkinson’s disease |
| title_short | Modulation of neuronal survival factor MEF2 by kinases in Parkinson’s disease |
| title_sort | modulation of neuronal survival factor mef2 by kinases in parkinson s disease |
| topic | Autophagy Mitochondria Parkinson's disease neurodegeneration kinase MEF2 |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00171/full |
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