title: Modeling Lewy pathology propagation in Parkinson's disease.
abstract: Lewy bodies (LBs) and Lewy neurites (LNs), comprised of alpha-synuclein (aSyn), are intraneuronal inclusions that characterize Parkinson's disease. Although the association between the extent of Lewy pathology and clinical symptoms is well established, how these proteinaceous deposits originate and target selectively vulnerable cell populations is unknown. Our knowledge of their role in PD pathogenesis is also limited. Here, we summarize recent findings demonstrating this pathology can be experimentally transmitted between animals by misfolded forms of aSyn that are capable of initiating and inducing LB and LN inclusion formation through a self-propagating mechanism reminiscent of prions. "Seeded" LBs and LNs in animal models also spread to multiple connected nuclei in a predictable pattern, recapitulating a phenomenon observed during human PD progression, leading to the dysfunction and degeneration of afflicted neurons. These models provide new perspectives on how this and other misfolded proteins may contribute to neurodegeneration in human disease.
authors.affiliation: Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia PA, 19104, USA. Electronic address: kelvincl@mail.med.upenn.edu.
authors.forename: Kelvin C
authors.initials: KC
authors.lastname: Luk
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
mesh_terms: D000818:Animals; D018450:Disease Progression; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology*; D020961:Lewy Body Disease; D008954:Models, Biological; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology*; D057165:Proteostasis Deficiencies / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: Parkinson's disease; Propagation; Protein misfolding; α-Synuclein