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.
References:
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.
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