Volpicelli-Daley LA, Luk KC, Patel TP, Tanik SA, Riddle DM, Stieber A, Meaney DF, Trojanowski JQ, Lee VM. Exogenous α-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron. 2011 Oct 6;72(1):57-71. PubMed.
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Massachusetts General Hospital/Harvard Medical School
I think this paper adds to the increasing literature on the consequences of extracellular α-synuclein and its role in PD pathogenesis. It represents an important validation of several recent studies showing that α-synuclein can be taken up by neurons from the extracellular space (Desplats et al., 2009; Danzer et al., 2011), that exogenously applied α-synuclein can seed aggregation of intracellular α-synuclein (Luk et al., 2009; Danzer et al., 2009), that α-synuclein oligomers can be transmitted from neuron to neuron and transported in both anterograde and retrograde direction within neurons (Danzer et al., 2011), and that extracellular α-synuclein can have detrimental effects in the recipient cells (Desplats et al., 2009; Emmanouilidou et al., 2010; Danzer et al., 2011). The paper is an important contribution to the field, demonstrating nicely how extracellular α-synuclein may be affecting neuronal cell health.
Desplats P, Lee HJ, Bae EJ, Patrick C, Rockenstein E, Crews L, Spencer B, Masliah E, Lee SJ. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13010-5. PubMed.
Danzer KM, Ruf WP, Putcha P, Joyner D, Hashimoto T, Glabe C, Hyman BT, McLean PJ. Heat-shock protein 70 modulates toxic extracellular α-synuclein oligomers and rescues trans-synaptic toxicity. FASEB J. 2011 Jan;25(1):326-36. PubMed.
Luk KC, Song C, O'Brien P, Stieber A, Branch JR, Brunden KR, Trojanowski JQ, Lee VM. Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20051-6. PubMed.
Danzer KM, Krebs SK, Wolff M, Birk G, Hengerer B. Seeding induced by alpha-synuclein oligomers provides evidence for spreading of alpha-synuclein pathology. J Neurochem. 2009 Oct;111(1):192-203. PubMed.
Emmanouilidou E, Melachroinou K, Roumeliotis T, Garbis SD, Ntzouni M, Margaritis LH, Stefanis L, Vekrellis K. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci. 2010 May 19;30(20):6838-51. PubMed.View all comments by Pam McClean
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