Activity depepdent regulation of alpha-synuclein release from neurons

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K20969
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology; Neurochemistry/Neuropharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: Yamada Kaoru 東京大学, 大学院医学系研究科(医学部), 助教 (00735152)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: α-synuclein / 伝播 / 神経活動

Outline of Final Research Achievements

The pathological aggregation of α-synuclein characterizes a set of neurodegenerative disorders collectively referred to as α-synucleinopathies.α-Synuclein is a cytoplasmic protein, however, it is actively released into the extracellular space. In this study, utilizing in vivo microdialysis and primary neuronal culture, we demonstrated that physiological release of a-synuclein highly depends on neuronal activity. Selective modulation of glutamatergic neurotransmission altered extracellular α-synuclein levels in freely moving mice. While neuronal activity tightly regulated α-synuclein release, elevated synaptic vesicle exocytosis per se sfficiently elicited α-synuclein release. We also found that extracellular α-synuclein in brain interstitial fluid existed as 60kda high molecular weight species.

Free Research Field

病態神経科学