title: Calcium: Alpha-Synuclein Interactions in Alpha-Synucleinopathies.
abstract: 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.
authors.affiliation: Menzies Health Institute Queensland, Griffith University Gold Coast, QLD, Australia.
authors.forename: Alexandre N
authors.initials: AN
authors.lastname: Rcom-H'cheo-Gauthier
authors.affiliation: Menzies Health Institute Queensland, Griffith University Gold Coast, QLD, Australia.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Osborne
authors.affiliation: Menzies Health Institute Queensland, Griffith University Gold Coast, QLD, Australia.
authors.forename: Adrian C B
authors.initials: AC
authors.lastname: Meedeniya
authors.affiliation: Menzies Health Institute Queensland, Griffith University Gold Coast, QLD, Australia.
authors.forename: Dean L
authors.initials: DL
authors.lastname: Pountney
keywords: Dementia with Lewy bodies; Multiple system atrophy; Parkinson's disease; calcium; α-Synuclein