title: Interactions between calcium and alpha-synuclein in neurodegeneration.
abstract: In Parkinson's disease and some atypical Parkinson's syndromes, aggregation of the α-synuclein protein (α-syn) has been linked to neurodegeneration. Many triggers for pathological α-syn aggregation have been identified, including port-translational modifications, oxidative stress and raised metal ions, such as Ca2+. Recently, it has been found using cell culture models that transient increases of intracellular Ca2+ induce cytoplasmic α-syn aggregates. Ca2+-dependent α-syn aggregation could be blocked by the Ca2+ buffering agent, BAPTA-AM, or by the Ca2+ channel blocker, Trimethadione. Furthermore, a greater proportion of cells positive for aggregates occurred when both raised Ca2+ and oxidative stress were combined, indicating that Ca2+ and oxidative stress cooperatively promote α-syn aggregation. Current on-going work using a unilateral mouse lesion model of Parkinson's disease shows a greater proportion of calbindin-positive neurons survive the lesion, with intracellular α-syn aggregates almost exclusively occurring in calbindin-negative neurons. These and other recent findings are reviewed in the context of neurodegenerative pathologies and suggest an association between raised Ca2+, α-syn aggregation and neurotoxicity.
authors.affiliation: Griffith Health Institute, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, Australia. alexandre.rcom-hcheo-gauthier@griffithuni.edu.au.
authors.forename: Alex
authors.initials: A
authors.lastname: Rcom-H'cheo-Gauthier
authors.affiliation: Griffith Health Institute, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, Australia. j.goodwin@griffith.edu.au.
authors.forename: Jacob
authors.initials: J
authors.lastname: Goodwin
authors.affiliation: Griffith Health Institute, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, Australia. d.pountney@griffith.edu.au.
authors.forename: Dean L
authors.initials: DL
authors.lastname: Pountney
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011485:Protein Binding; D055503:Protein Multimerization; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein; D002118:Calcium