title: A critical review of the development and importance of proteinaceous aggregates in animal models of Parkinson's disease: new insights into Lewy body formation.
abstract: The pace of development of new animal models of Parkinson's disease (PD) has increased dramatically in the recent past, primarily because of the identification of the protein, alpha-synuclein, in Lewy bodies in both idiopathic and familial PD. This discovery has allowed the production of transgenic models that incorporate a form of human, mutant alpha-synuclein from rare familial cases, and has enabled the search for Lewy-body-like aggregations of this protein in toxin-induced models. Indeed, alpha-synuclein-positive inclusions, some of which bear strong resemblance to Lewy bodies, have now been recognized and their formation investigated in several different, environmentally-induced and transgenic models. Nevertheless, these data have yet to provide a uniform theory of inclusion pathogenesis for PD. The aim of this review is not only to summarize the findings to date on alpha-synuclein-immunopositive inclusion bodies, including some new information on Lewy bodies, but also provide a concise viewpoint on their origin and formation in animal models. We will provide evidence for a predicted series of intracellular events that underlie inclusion formation. Triggered by oxidative and metabolic stress, chronic, toxin-treated animals, rather than transgenic models transfected with human alpha-synuclein, eventually produce inclusion bodies that most closely resemble early stages of Lewy bodies. Elucidating the common mechanisms in animal models is a first step towards understanding the role of Lewy bodies and their formation in Parkinson's disease.
authors.affiliation: Department of Cellular and Molecular Pharmacology, Chicago Medical School, Finch University of Health Sciences, 3333 Green Bay Road, North Chicago, IL 60054, USA. gloria.meredith@finchcms.edu
authors.forename: Gloria E
authors.initials: GE
authors.lastname: Meredith
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.forename: Susan
authors.initials: S
authors.lastname: Totterdell
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D016631:Lewy Bodies / Q000473:pathology*; D010300:Parkinson Disease / Q000473:pathology*; D011506:Proteins
chemical_list: D011506:Proteins