How can rAAV-α-synuclein and the fibril α-synuclein models advance our understanding of Parkinson's disease?

New insights into cellular α-synuclein homeostasis in health and disease

(2016) Ulf Dettmer et al.   CURRENT OPINION IN NEUROBIOLOGY

Invisible Killers

(2016) Laura A. Volpicelli-Daley et al.   MOVEMENT DISORDERS

Direct visualization of alpha-synuclein oligomers reveals previously undetected pathology in Parkinson’s disease brain

(2015) Rosalind F. Roberts et al.   BRAIN

Depressive-like phenotype induced by AAV-mediated overexpression of human α-synuclein in midbrain dopaminergic neurons

(2015) D. Caudal et al.   EXPERIMENTAL NEUROLOGY

Dopamine Transporter Activity Is Modulated by α-Synuclein

(2015) Brittany Butler et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates α-Synuclein Gene-induced Neurodegeneration

(2015) João P. L. Daher et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Trib3 Is Elevated in Parkinson's Disease and Mediates Death in Parkinson's Disease Models

(2015) P. Aime et al.   JOURNAL OF NEUROSCIENCE

Nigral overexpression of alpha-synuclein in the absence of parkin enhances alpha-synuclein phosphorylation but does not modulate dopaminergic neurodegeneration

(2015) Anne-Sophie Van Rompuy et al.   Molecular Neurodegeneration

Trophic factors for Parkinson's disease: To live or let die

(2015) C. Warren Olanow et al.   MOVEMENT DISORDERS

α-Synuclein strains cause distinct synucleinopathies after local and systemic administration

(2015) W. Peelaerts et al.   NATURE

Structure of the toxic core of α-synuclein from invisible crystals

(2015) Jose A. Rodriguez et al.   NATURE

The loss of glucose-regulated protein 78 (GRP78) during normal aging or from siRNA knockdown augments human alpha-synuclein (α-syn) toxicity to rat nigral neurons

(2015) Maxim Salganik et al.   NEUROBIOLOGY OF AGING

α-Synuclein-induced dopaminergic neurodegeneration in a rat model of Parkinson's disease occurs independent of ATP13A2 (PARK9)

(2015) Guillaume Daniel et al.   NEUROBIOLOGY OF DISEASE

Intrastriatal injection of pre-formed mouse α-synuclein fibrils into rats triggers α-synuclein pathology and bilateral nigrostriatal degeneration

(2015) Katrina L. Paumier et al.   NEUROBIOLOGY OF DISEASE

Glucocerebrosidase gene therapy prevents α-synucleinopathy of midbrain dopamine neurons

(2015) Emily M. Rocha et al.   NEUROBIOLOGY OF DISEASE

Parkinson-causing α-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation

(2015) Ulf Dettmer et al.   Nature Communications

Progressive Aggregation of Alpha-Synuclein and Selective Degeneration of Lewy Inclusion-Bearing Neurons in a Mouse Model of Parkinsonism

(2015) Valerie R. Osterberg et al.   Cell Reports

Lack of additive role of ageing in nigrostriatal neurodegeneration triggered by α-synuclein overexpression

(2015) Mathieu Bourdenx et al.   Acta Neuropathologica Communications

Targeted Overexpression of α-Synuclein by rAAV2/1 Vectors Induces Progressive Nigrostriatal Degeneration and Increases Vulnerability to MPTP in Mouse

(2015) Lian-Kun Song et al.   PLoS One

Fractalkine Signaling Regulates the Inflammatory Response in an α-Synuclein Model of Parkinson Disease

(2015) Aaron D. Thome et al.   PLoS One

Formation of α-synuclein Lewy neurite–like aggregates in axons impedes the transport of distinct endosomes

(2014) Laura A. Volpicelli-Daley et al.   MOLECULAR BIOLOGY OF THE CELL

Ten Years and Counting: Moving Leucine-Rich RepeatKinase 2 Inhibitors to the Clinic

(2014) Andrew B. West   MOVEMENT DISORDERS

Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

(2014) Mike A Nalls et al.   NATURE GENETICS

Addition of exogenous α-synuclein preformed fibrils to primary neuronal cultures to seed recruitment of endogenous α-synuclein to Lewy body and Lewy neurite–like aggregates

(2014) Laura A Volpicelli-Daley et al.   Nature Protocols

The ongoing pursuit of neuroprotective therapies in Parkinson disease

(2014) Dilan Athauda et al.   Nature Reviews Neurology

Enhanced ubiquitin-dependent degradation by Nedd4 protects against α-synuclein accumulation and toxicity in animal models of Parkinson's disease

(2014) Sian E. Davies et al.   NEUROBIOLOGY OF DISEASE

Differential Expression of Alpha-Synuclein in Hippocampal Neurons

(2014) Katsutoshi Taguchi et al.   PLoS One

Abrogation of  -synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats

(2014) J. P. L. Daher et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

α-Synuclein assembles into higher-order multimers upon membrane binding to promote SNARE complex formation

(2014) Jacqueline Burré et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

α-Synuclein Immunotherapy Blocks Uptake and Templated Propagation of Misfolded α-Synuclein and Neurodegeneration

(2014) Hien T. Tran et al.   Cell Reports

Pathological alpha-synuclein propagates through neural networks

(2014) Masami Masuda-Suzukake et al.   Acta Neuropathologica Communications

Boosting chaperone-mediated autophagy in vivo mitigates α-synuclein-induced neurodegeneration

(2013) Maria Xilouri et al.   BRAIN

Prion-like spreading of pathological α-synuclein in brain

(2013) Masami Masuda-Suzukake et al.   BRAIN

Disease duration and the integrity of the nigrostriatal system in Parkinson’s disease

(2013) Jeffrey H. Kordower et al.   BRAIN

MHCII Is Required for  -Synuclein-Induced Activation of Microglia, CD4 T Cell Proliferation, and Dopaminergic Neurodegeneration

(2013) A. S. Harms et al.   JOURNAL OF NEUROSCIENCE

Calcium Entry and  -Synuclein Inclusions Elevate Dendritic Mitochondrial Oxidant Stress in Dopaminergic Neurons

(2013) D. I. Dryanovski et al.   JOURNAL OF NEUROSCIENCE

rAAV2/7 vector-mediated overexpression of alpha-synuclein in mouse substantia nigra induces protein aggregation and progressive dose-dependent neurodegeneration

(2013) Marusela Oliveras-Salvá et al.   Molecular Neurodegeneration

Neuronal vulnerability, pathogenesis, and Parkinson's disease

(2013) David Sulzer et al.   MOVEMENT DISORDERS

The many faces of alpha-synuclein mutations

(2013) Meike Kasten et al.   MOVEMENT DISORDERS

Characterization of Cognitive Deficits in Rats Overexpressing Human Alpha-Synuclein in the Ventral Tegmental Area and Medial Septum Using Recombinant Adeno-Associated Viral Vectors

(2013) Hélène Hall et al.   PLoS One

Morphological and Behavioral Impact of AAV2/5-Mediated Overexpression of Human Wildtype Alpha-Synuclein in the Rat Nigrostriatal System

(2013) Sara E. Gombash et al.   PLoS One

TFEB-mediated autophagy rescues midbrain dopamine neurons from  -synuclein toxicity

(2013) M. Decressac et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds

(2013) B. B. Holmes et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Identification and Rescue of  -Synuclein Toxicity in Parkinson Patient-Derived Neurons

(2013) C. Y. Chung et al.   SCIENCE

Yeast Reveal a "Druggable" Rsp5/Nedd4 Network that Ameliorates  -Synuclein Toxicity in Neurons

(2013) D. F. Tardiff et al.   SCIENCE

Structural and functional characterization of two alpha-synuclein strains

(2013) Luc Bousset et al.   Nature Communications

Nigrostriatal overabundance of α-synuclein leads to decreased vesicle density and deficits in dopamine release that correlate with reduced motor activity

(2012) Meret Nora Gaugler et al.   ACTA NEUROPATHOLOGICA

A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB

(2012) Carmine Settembre et al.   EMBO JOURNAL

Comparison of the behavioural and histological characteristics of the 6-OHDA and α-synuclein rat models of Parkinson's disease

(2012) M. Decressac et al.   EXPERIMENTAL NEUROLOGY

Dysregulated dopamine storage increases the vulnerability to α-synuclein in nigral neurons

(2012) Ayse Ulusoy et al.   NEUROBIOLOGY OF DISEASE

Impaired neurotransmission caused by overexpression of  -synuclein in nigral dopamine neurons

(2012) M. Lundblad et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Pathological  -Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice

(2012) K. C. Luk et al.   SCIENCE

 -Synuclein-Induced Down-Regulation of Nurr1 Disrupts GDNF Signaling in Nigral Dopamine Neurons

(2012) M. Decressac et al.   Science Translational Medicine

Aggregation of αSynuclein promotes progressive in vivo neurotoxicity in adult rat dopaminergic neurons

(2011) Grit Taschenberger et al.   ACTA NEUROPATHOLOGICA

GDNF fails to exert neuroprotection in a rat  -synuclein model of Parkinson's disease

(2011) M. Decressac et al.   BRAIN

Elevated tonic extracellular dopamine concentration and altered dopamine modulation of synaptic activity precede dopamine loss in the striatum of mice overexpressing human α-synuclein

(2011) Hoa A. Lam et al.   JOURNAL OF NEUROSCIENCE RESEARCH

Progressive neurodegenerative and behavioural changes induced by AAV-mediated overexpression of α-synuclein in midbrain dopamine neurons

(2011) M. Decressac et al.   NEUROBIOLOGY OF DISEASE

Exogenous α-Synuclein Fibrils Induce Lewy Body Pathology Leading to Synaptic Dysfunction and Neuron Death

(2011) Laura A. Volpicelli-Daley et al.   NEURON

Progressive Neurodegeneration or Endogenous Compensation in an Animal Model of Parkinson's Disease Produced by Decreasing Doses of Alpha-Synuclein

(2011) James B. Koprich et al.   PLoS One

Genome-Wide Association Study Confirms SNPs inSNCAand theMAPTRegion as Common Risk Factors for Parkinson Disease

(2010) Todd L. Edwards et al.   ANNALS OF HUMAN GENETICS

Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial

(2010) William J Marks et al.   LANCET NEUROLOGY

Expression of human A53T alpha-synuclein in the rat substantia nigra using a novel AAV1/2 vector produces a rapidly evolving pathology with protein aggregation, dystrophic neurite architecture and nigrostriatal degeneration with potential to model the pathology of Parkinson's disease

(2010) James B Koprich et al.   Molecular Neurodegeneration

Fcγ receptors are required for NF-κB signaling, microglial activation and dopaminergic neurodegeneration in an AAV-synuclein mouse model of Parkinson's disease

(2010) Shuwen Cao et al.   Molecular Neurodegeneration

α-Synuclein Expression in Rat Substantia Nigra Suppresses Phospholipase D2 Toxicity and Nigral Neurodegeneration

(2010) Oleg S Gorbatyuk et al.   MOLECULAR THERAPY

Parkinson's disease, primates, and gene therapy: Vive la différence?

(2010) Travis B. Lewis et al.   MOVEMENT DISORDERS

Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease

(2010) Taye H Hamza et al.   NATURE GENETICS

Microglia Acquire Distinct Activation Profiles Depending on the Degree of α-Synuclein Neuropathology in a rAAV Based Model of Parkinson's Disease

(2010) Vanesa Sanchez-Guajardo et al.   PLoS One

Comparison of transduction efficiency of recombinant AAV serotypes 1, 2, 5, and 8 in the rat nigrostriatal system

(2009) Nikolaus R. McFarland et al.   JOURNAL OF NEUROCHEMISTRY

α-Synuclein S129 Phosphorylation Mutants Do Not Alter Nigrostriatal Toxicity in a Rat Model of Parkinson Disease

(2009) Nikolaus R. McFarland et al.   JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY

Dynamic Changes in Presynaptic and Axonal Transport Proteins Combined with Striatal Neuroinflammation Precede Dopaminergic Neuronal Loss in a Rat Model of AAV  -Synucleinopathy

(2009) C. Y. Chung et al.   JOURNAL OF NEUROSCIENCE

Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease

(2009) Wataru Satake et al.   NATURE GENETICS

Genome-wide association study reveals genetic risk underlying Parkinson's disease

(2009) Javier Simón-Sánchez et al.   NATURE GENETICS

Genomewide association study for susceptibility genes contributing to familial Parkinson disease

(2008) Nathan Pankratz et al.   HUMAN GENETICS

Targeted Overexpression of Human α-Synuclein Triggers Microglial Activation and an Adaptive Immune Response in a Mouse Model of Parkinson Disease

(2008) Shaji Theodore et al.   JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY

Strengths and limitations of genetic mouse models of Parkinson's disease

(2008) Marie-Francoise Chesselet et al.   PARKINSONISM & RELATED DISORDERS

The phosphorylation state of Ser-129 in human  -synuclein determines neurodegeneration in a rat model of Parkinson disease

(2008) O. S. Gorbatyuk et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

In vivo alpha-synuclein overexpression in rodents: A useful model of Parkinson's disease?

(2007) Marie-Francoise Chesselet   EXPERIMENTAL NEUROLOGY

In vivo gene delivery for development of mammalian models for Parkinson's disease

(2007) Ayse Ulusoy et al.   EXPERIMENTAL NEUROLOGY