title: α-Synuclein-Based Animal Models of Parkinson's Disease: Challenges and Opportunities in a New Era.
abstract: In recent years, a new generation of animal models of Parkinson's disease (PD) based on ectopic expression, overexpression, or intracerebral injection of the protein α-synuclein have emerged. Critically, these models develop inclusions of aggregated α-synuclein and/or α-synuclein-mediated neuronal loss replicating the defining pathological hallmarks of PD and driving significant advances in the understanding of the pathogenic mechanisms underpinning PD. Here, we provide a comprehensive review of this new generation of animal models of PD, ranging from invertebrate to rodent to nonhuman primate. We focus on their strengths and limitations with respect to their highly anticipated contribution to the further understanding of α-synuclein pathobiology and the future testing of novel disease-modifying therapeutics.
authors: Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, ONT, Canada. Electronic address: naomi.visanji@uhnresearch.ca.
authors: Naomi P
authors: NP
authors: Visanji
authors: The Krembil Institute, University Health Network, Toronto, ONT, Canada.
authors: Jonathan M
authors: JM
authors: Brotchie
authors: Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, ONT, Canada; The Krembil Institute, University Health Network, Toronto, ONT, Canada; Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ONT, Canada; Department of Medicine, University of Toronto, Toronto, ONT, Canada.
authors: Lorraine V
authors: LV
authors: Kalia
authors: The Krembil Institute, University Health Network, Toronto, ONT, Canada.
authors: James B
authors: JB
authors: Koprich
authors: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ONT, Canada; Department of Medicine, University of Toronto, Toronto, ONT, Canada.
authors: Anurag
authors: A
authors: Tandon
authors: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ONT, Canada; Department of Biochemistry, University of Toronto, Toronto, ONT, Canada.
authors: Joel C
authors: JC
authors: Watts
authors: Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, ONT, Canada; The Krembil Institute, University Health Network, Toronto, ONT, Canada; Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ONT, Canada; Department of Medicine, University of Toronto, Toronto, ONT, Canada.
authors: Anthony E
authors: AE
authors: Lang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D055808:Drug Discovery; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology*; D011328:Prions / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D011328:Prions; D051844:alpha-Synuclein
keywords: Parkinson's disease; alpha synuclein; animal models; drug development; prion; transgenic