Extracellular neurosin degrades α-synuclein in cultured cells

Tatebe, Harutsugu; Watanabe, Yoshihisa; Kasai, Takashi; Mizuno, Toshiki; Nakagawa, Masanori; Tanaka, Masaki; Tokuda, Takahiko

doi:10.1016/j.neures.2010.04.008

Cited by 72 publications

(81 citation statements)

References 27 publications

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“…In the context of cell-mediated clearance, it was reported that extracellular ␣-syn could be cleared by neighboring cells such as neurons, astrocytes and microglia (17). In addition, in the context of proteolytic degradation, it was also reported that neurosin (33) and matrix metalloproteinases (MMPs) (34) could degrade extracellular ␣-syn.…”

Section: Parkinson Disease (Pd)mentioning

confidence: 99%

Proteolytic Cleavage of Extracellular α-Synuclein by Plasmin

Kim

Choi

Park

et al. 2012

Journal of Biological Chemistry

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Background: A prion-like spread of ␣-synuclein might play a role in the pathogenesis of Parkinson disease. Results: Extracellular ␣-synuclein was cleaved by plasmin. Cultured microglia and astrocytes did not take up plasmin digested extracellular ␣-synuclein, and were not activated. Conclusion: Plasmin-mediated ␣-synuclein clearance problems might play a role in the pathogenesis of Parkinson disease. Significance: Therapies aimed at ␣-synuclein clearance may lead to new therapies for Parkinson disease.

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Section: Parkinson Disease (Pd)mentioning

confidence: 99%

Proteolytic Cleavage of Extracellular α-Synuclein by Plasmin

Kim

Choi

Park

et al. 2012

Journal of Biological Chemistry

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“…In vitro, it was found that neurosin prevented alpha-synuclein polymerization by reducing the amount of monomer and also by generating fragmented alpha-synucleins that themselves inhibited the polymerization. In the presence of cellular stress, the mitochondria keep on releasing neurosin to the cytosol, causing an increase in degraded alpha-synuclein species (Tatebe et al, 2010;Iwata et al, 2003). Down-regulation of neurosin causes accumulation of alpha-synuclein (Xilouri et al, 2013).…”

Section: Mutations Of Alpha-synuclein Can Cause Mitochondrial Damagementioning

confidence: 99%

The possible involvement of mitochondrial dysfunctions in Lewy body dementia: a systematic review

Spano¹,

Signorelli²,

Vitaliani³

et al. 2015

Functional Neurology

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SummaryThe hallmark of dementia with Lewy bodies (DLB) is the "Lewy body", an abnormal aggregation of alphasynuclein found in some areas of the brain. The brain is the organ/system that is most vulnerable to this oxidative damage, and reactive oxygen species can cause neurodegenerative diseases. Different models of mitochondrial deregulation have been compared in DLB. The results are consistent with the hypothesis that alpha-synuclein affects the mitochondria themselves, increasing their sensitivity or leading to cell death through protective (neurosin) and accelerating (cytochrome c) factors. This systematic review suggests that mitochondria play an important role in neurodegeneration and a crucial role in the formation of Lewy bodies. DLB is a disease characterized by abnormal accumulation of alpha-synuclein that could result in the release of cytochrome c and subsequent activation of the apoptotic cascade.

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“…55 Tatebe et al later demonstrated in vitro that secreted neurosin degrades extracellular α-syn. 61 Recently, the viral mediated delivery of neurosin has been shown to promote the clearance of α-syn and reduces pathology in an α-syn model, 62 implying that neurosin may be a new therapeutic target for PD.…”

Section: Other Clearance Systems As Therapeutic Approaches Against Pdmentioning

confidence: 99%