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KMID : 0043320210440060564
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Archives of Pharmacal Research
2021 Volume.44 No. 6 p.564 ~ p.573
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Complicity of α-synuclein oligomer and calcium dyshomeostasis in selective neuronal vulnerability in Lewy body disease
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Yamamoto Kenji
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Abstract
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α-Synuclein oligomers and Ca2+ dyshomeostasis have been thoroughly investigated with respect to the pathogenesis of Lewy body disease (LBD). In LBD, α-synuclein oligomers exhibit a neuron-specific cytoplasmic distribution. Highly active neurons and neurons with a high Ca2+ burden are prone to damage in LBD. The neuronal vulnerability may be determined by transneuronal axonal transmission of the pathological processes; however, this hypothesis seems inconsistent with pathological findings that neurons anatomically connected to LBD-vulnerable neurons, such as neurons in the ventral tegmentum, are spared in LBD. This review focuses on and discusses the crucial roles played by α-synuclein oligomers and Ca2+ dyshomeostasis in early intraneural pathophysiology in LBD-vulnerable neurons. A challenging view is proposed on the synergy between retrograde transport of α-synuclein and vesicular Ca release, whereby neuronal vulnerability is propagated backward along repeatedly activated signaling pathway.
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KEYWORD
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Parkinson’s disease, Dementia with Lewy body, α-Synuclein oligomers, Calcium dysregulation, Calcium binding protein, Selective neuronal degeneration
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