Author:
Awa Shiori,Suzuki Genjiro,Masuda-Suzukake Masami,Nonaka Takashi,Saito Minoru,Hasegawa Masato
Abstract
AbstractAccumulation of phosphorylated α-synuclein aggregates has been implicated in several diseases, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and is thought to spread in a prion-like manner. Elucidating the mechanisms of prion-like transmission of α-synuclein is important for the development of therapies for these diseases, but little is known about the details. Here, we injected α-synuclein fibrils into the brains of wild-type mice and examined the early phase of the induction of phosphorylated α-synuclein accumulation. We found that phosphorylated α-synuclein appeared within a few days after the intracerebral injection. It was observed initially in presynaptic regions and subsequently extended its localization to axons and cell bodies. These results suggest that extracellular α-synuclein fibrils are taken up into the presynaptic region and seed-dependently convert the endogenous normal α-synuclein that is abundant there to an abnormal phosphorylated form, which is then transported through the axon to the cell body.
Funder
Japan Society for the Promotion of Science
Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care
Takeda Science Foundation
Core Research for Evolutional Science and Technology
Japan Agency for Medical Research and Development
Publisher
Springer Science and Business Media LLC
Cited by
16 articles.
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