Calcium: Alpha-Synuclein Interactions in Alpha-Synucleinopathies
Autor: | Alexandre N. Rcom-H'cheo-Gauthier, Samantha L. Osborne, Adrian Cuda Banda Meedeniya, Dean Louis Pountney |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Mini Review Parkinson's disease Calcium buffering Dementia with Lewy bodies chemistry.chemical_element α-synuclein2 Multiple system atrophy4 Biology Calcium medicine.disease_cause Inclusion bodies lcsh:RC321-571 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Calcium3 lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Synucleinopathies Alpha-synuclein α-Synuclein calcium General Neuroscience Calcium channel Neurotoxicity Multiple system atrophy medicine.disease Cell biology Parkinson’s disease1 nervous system diseases 030104 developmental biology Dementia with Lewy Bodies5 Biochemistry chemistry nervous system 030217 neurology & neurosurgery Oxidative stress Neuroscience |
Zdroj: | Frontiers in Neuroscience Frontiers in Neuroscience, Vol 10 (2016) |
ISSN: | 1662-453X 1662-4548 |
Popis: | Aggregation of the pre-synaptic protein, α-synuclein (α-syn), is the key etiological factor in Parkinson's disease (PD) and other alpha-synucleinopathies, such as multiple system atrophy (MSA) and Dementia with Lewy bodies (DLB). Various triggers for pathological α-syn aggregation have been elucidated, including post-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. |
Databáze: | OpenAIRE |
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