Calcium: alpha-synuclein interactions in alpha-synucleinopathies
Aggregation of the pre-synaptic protein, α-synuclein (α-syn), is the key aetiological factor in Parkinson’s disease (PD) and other alpha-synucleinopathies, such as multiple system atrophy and Dementia with Lewy bodies. Various triggers for pathological α-syn aggregation have been elucidated, includi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-12-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00570/full |
| _version_ | 1819094512137404416 |
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| author | Alexandre N. Rcom-H’cheo-Gauthier1 Samantha L. Osborne Adrian C.B. Meedneniya Dean Louis Pountney |
| author_facet | Alexandre N. Rcom-H’cheo-Gauthier1 Samantha L. Osborne Adrian C.B. Meedneniya Dean Louis Pountney |
| author_sort | Alexandre N. Rcom-H’cheo-Gauthier1 |
| collection | DOAJ |
| description | Aggregation of the pre-synaptic protein, α-synuclein (α-syn), is the key aetiological factor in Parkinson’s disease (PD) and other alpha-synucleinopathies, such as multiple system atrophy and Dementia with Lewy bodies. Various triggers for pathological α-syn aggregation have been elucidated, including port-translational modifications, oxidative stress and binding of metal ions, such as calcium. Raised neuronal calcium levels in PD may occur due to mitochondrial dysfunction and/or may relate to calcium channel dysregulation or the reduced expression of the neuronal calcium buffering protein, calbindin-D28k. Recent results on human tissue and a mouse oxidative stress model show that neuronal calbindin-D28k expression excludes α-syn inclusion bodies. Previously, cell culture model studies have shown that transient increases of intracellular free Ca(II), such as by opening of the voltage-gated plasma calcium channels, could induce cytoplasmic aggregates of α-syn. Raised intracellular free calcium and oxidative stress also act cooperatively to promote α-syn aggregation. The association between raised neuronal calcium, α-syn aggregation, oxidative stress and neurotoxicity is reviewed in the context of neurodegenerative α-syn disease and potential mechanism-based therapies. |
| first_indexed | 2024-12-21T23:28:35Z |
| format | Article |
| id | doaj.art-351dd0240ea3480c9c5cbe71f340332a |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-21T23:28:35Z |
| publishDate | 2016-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-351dd0240ea3480c9c5cbe71f340332a2022-12-21T18:46:34ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2016-12-011010.3389/fnins.2016.00570233634Calcium: alpha-synuclein interactions in alpha-synucleinopathiesAlexandre N. Rcom-H’cheo-Gauthier10Samantha L. Osborne1Adrian C.B. Meedneniya2Dean Louis Pountney3Griffith UniversityGriffith UniversityGriffith UniversityGriffith UniversityAggregation of the pre-synaptic protein, α-synuclein (α-syn), is the key aetiological factor in Parkinson’s disease (PD) and other alpha-synucleinopathies, such as multiple system atrophy and Dementia with Lewy bodies. Various triggers for pathological α-syn aggregation have been elucidated, including port-translational modifications, oxidative stress and binding of metal ions, such as calcium. Raised neuronal calcium levels in PD may occur due to mitochondrial dysfunction and/or may relate to calcium channel dysregulation or the reduced expression of the neuronal calcium buffering protein, calbindin-D28k. Recent results on human tissue and a mouse oxidative stress model show that neuronal calbindin-D28k expression excludes α-syn inclusion bodies. Previously, cell culture model studies have shown that transient increases of intracellular free Ca(II), such as by opening of the voltage-gated plasma calcium channels, could induce cytoplasmic aggregates of α-syn. Raised intracellular free calcium and oxidative stress also act cooperatively to promote α-syn aggregation. The association between raised neuronal calcium, α-syn aggregation, oxidative stress and neurotoxicity is reviewed in the context of neurodegenerative α-syn disease and potential mechanism-based therapies.http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00570/fullParkinson’s disease1α-synuclein2Calcium3Multiple system atrophy4Dementia with Lewy Bodies5. |
| spellingShingle | Alexandre N. Rcom-H’cheo-Gauthier1 Samantha L. Osborne Adrian C.B. Meedneniya Dean Louis Pountney Calcium: alpha-synuclein interactions in alpha-synucleinopathies Frontiers in Neuroscience Parkinson’s disease1 α-synuclein2 Calcium3 Multiple system atrophy4 Dementia with Lewy Bodies5. |
| title | Calcium: alpha-synuclein interactions in alpha-synucleinopathies |
| title_full | Calcium: alpha-synuclein interactions in alpha-synucleinopathies |
| title_fullStr | Calcium: alpha-synuclein interactions in alpha-synucleinopathies |
| title_full_unstemmed | Calcium: alpha-synuclein interactions in alpha-synucleinopathies |
| title_short | Calcium: alpha-synuclein interactions in alpha-synucleinopathies |
| title_sort | calcium alpha synuclein interactions in alpha synucleinopathies |
| topic | Parkinson’s disease1 α-synuclein2 Calcium3 Multiple system atrophy4 Dementia with Lewy Bodies5. |
| url | http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00570/full |
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