The role of α-synuclein in Parkinson's disease: insights from animal models

Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease

1997 • 7,814 citations

The Genome Sequence of Drosophila melanogaster

2000 • 5,882 citations

Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism

1998 • 5,063 citations

Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis

1983 • 4,822 citations

Chronic systemic pesticide exposure reproduces features of Parkinson's disease

2000 • 3,559 citations

AGEING AND PARKINSON'S DISEASE: SUBSTANTIA NIGRA REGIONAL SELECTIVITY

1991 • 3,275 citations

Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism

2003 • 2,691 citations

A Drosophila model of Parkinson's disease

2000 • 2,062 citations

α-Synuclein is phosphorylated in synucleinopathy lesions

2002 • 1,868 citations

Dopaminergic Loss and Inclusion Body Formation in α-Synuclein Mice: Implications for Neurodegenerative Disorders

2000 • 1,729 citations

Mice Lacking α-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine System

2000 • 1,628 citations

Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies.

1998 • 1,546 citations

Acceleration of oligomerization, not fibrillization, is a shared property of both α-synuclein mutations linked to early-onset Parkinson's disease: Implications for pathogenesis and therapy

2000 • 1,497 citations

Accelerated in vitro fibril formation by a mutant α-synuclein linked to early-onset Parkinson disease

1998 • 1,460 citations

Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology

1997 • 1,438 citations

Amyloid pores from pathogenic mutations

2002 • 1,260 citations

Generation of reactive oxygen species by the mitochondrial electron transport chain

2002 • 1,208 citations

Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants

2003 • 1,156 citations

Neuronal α-Synucleinopathy with Severe Movement Disorder in Mice Expressing A53T Human α-Synuclein

2002 • 1,152 citations

Kinetic Stabilization of the α-Synuclein Protofibril by a Dopamine-α-Synuclein Adduct

2001 • 1,116 citations

Ubiquitination of a New Form of α-Synuclein by Parkin from Human Brain: Implications for Parkinson's Disease

2001 • 1,036 citations

Filamentous α-synuclein inclusions link multiple system atrophy with Parkinson's disease and dementia with Lewy bodies

1998 • 949 citations

Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70

1999 • 830 citations

Characterization of a novel protein regulated during the critical period for song learning in the zebra finch

1995 • 826 citations

Synaptic Vesicle Depletion Correlates with Attenuated Synaptic Responses to Prolonged Repetitive Stimulation in Mice Lacking α-Synuclein

2002 • 817 citations

The UCH-L1 Gene Encodes Two Opposing Enzymatic Activities that Affect α-Synuclein Degradation and Parkinson's Disease Susceptibility

2002 • 768 citations

Human α-synuclein-harboring familial Parkinson's disease-linked Ala-53 → Thr mutation causes neurodegenerative disease with α-synuclein aggregation in transgenic mice

2002 • 760 citations

Dopamine-dependent neurotoxicity of α-synuclein: A mechanism for selective neurodegeneration in Parkinson disease

2002 • 722 citations

α-Synuclein Fibrillogenesis Is Nucleation-dependent

1999 • 686 citations

Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system.

2002 • 642 citations

The risk of Parkinson's disease with exposure to pesticides, farming, well water, and rural living

1998 • 630 citations

A role for alpha-synuclein in the regulation of dopamine biosynthesis.

2002 • 629 citations

Experimental models of Parkinson's disease

2001 • 617 citations

Animal models of Parkinson's disease

2002 • 580 citations

Parkinson-Like Neurodegeneration Induced by Targeted Overexpression of α-Synuclein in the Nigrostriatal System

2002 • 577 citations

Resistance of α-synuclein null mice to the parkinsonian neurotoxin MPTP

2002 • 569 citations

A Role for α-Synuclein in the Regulation of Dopamine Biosynthesis

2002 • 545 citations

α-Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson's disease

2002 • 511 citations

Neuropathology in mice expressing human alpha-synuclein.

2000 • 499 citations

The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity.

2000 • 483 citations

Vesicle Permeabilization by Protofibrillar α-Synuclein Is Sensitive to Parkinson's Disease-Linked Mutations and Occurs by a Pore-like Mechanism

2002 • 470 citations

Neuropathology in Mice Expressing Human α-Synuclein

2000 • 456 citations

The A53T α-Synuclein Mutation Increases Iron-Dependent Aggregation and Toxicity

2000 • 445 citations

β-Synuclein Inhibits α-Synuclein Aggregation

2001 • 401 citations

Nigrostriatal α-synucleinopathy induced by viral vector-mediated overexpression of human α-synuclein: A new primate model of Parkinson's disease

2003 • 393 citations

Parkin Suppresses Dopaminergic Neuron-Selective Neurotoxicity Induced by Pael-R in Drosophila

2003 • 359 citations

Aggregates from mutant and wild‐type α‐synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β‐sheet and amyloid‐like filaments

1998 • 357 citations

Parkin Localizes to the Lewy Bodies of Parkinson Disease and Dementia with Lewy Bodies

2002 • 315 citations

Parkinson's disease, pesticides, and glutathione transferase polymorphisms

1998 • 314 citations

The 1.1-Å resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease

2003 • 300 citations

DJ-1 is an indicator for endogenous reactive oxygen species elicited by endotoxin

2001 • 286 citations

Behavioral and Neurochemical Effects of Wild-Type and Mutated Human α-Synuclein in Transgenic Mice

2002 • 280 citations

Lack of Nigral Pathology in Transgenic Mice Expressing Human α-Synuclein Driven by the Tyrosine Hydroxylase Promoter

2001 • 279 citations

MPTP induces alpha-synuclein aggregation in the substantia nigra of baboons

2000 • 277 citations

Synphilin-1 is present in Lewy bodies in Parkinson's disease

2000 • 261 citations

Oxidized forms of peroxiredoxins and DJ-1 on two-dimensional gels increased in response to sublethal levels of paraquat

2001 • 258 citations

Formation of hydrogen peroxide and hydroxyl radicals from Aβ and α-synuclein as a possible mechanism of cell death in Alzheimer’s disease and Parkinson’s disease 1,2 1This article is part of a series of reviews on “Causes and Consequences of Oxidative Stress in Alzheimer’s Disease.” The full list of papers may be found on the homepage of the journal. 2Guest Editors: Mark A. Smith and George Perry

2002 • 254 citations

Human α-Synuclein over-expression increases intracellular reactive oxygen species levels and susceptibility to dopamine

2002 • 242 citations

Selective Insolubility of α-Synuclein in Human Lewy Body Diseases Is Recapitulated in a Transgenic Mouse Model

2001 • 238 citations

L166P Mutant DJ-1, Causative for Recessive Parkinson's Disease, Is Degraded through the Ubiquitin-Proteasome System

2003 • 234 citations

Recent advances in the genetics and pathogenesis of Parkinson disease

2002 • 224 citations

Inhibition of Fibrillization and Accumulation of Prefibrillar Oligomers in Mixtures of Human and Mouse α-Synuclein

2000 • 221 citations

Accelerated Oligomerization by Parkinson's Disease Linked α‐Synuclein Mutants

2000 • 213 citations

Chaperoning brain degeneration

2002 • 208 citations

Dopaminergic Cell Loss Induced by Human A30P α-Synuclein Gene Transfer to the Rat Substantia Nigra

2002 • 208 citations

Lysosomal malfunction accompanies alpha-synuclein aggregation in a progressive mouse model of Parkinson’s disease

2002 • 203 citations

Full length article

1997 • 173 citations

Mitochondrial respiratory failure in skeletal muscle from patients with Parkinson's disease and multiple system atrophy

1994 • 170 citations

The mouse MPTP model: gene expression changes in dopaminergic neurons

2003 • 165 citations

14-3-3 Proteins in Lewy Bodies in Parkinson Disease and Diffuse Lewy Body Disease Brains

2002 • 163 citations

Neuroprotective and neurorestorative strategies for Parkinson's disease

2002 • 162 citations

Parkin and the Molecular Pathways of Parkinson's Disease

2001 • 160 citations

Effects of Pharmacological Agents upon a Transgenic Model of Parkinson's Disease in Drosophila melanogaster

2002 • 159 citations

β-Synuclein Inhibits Formation of α-Synuclein Protofibrils: A Possible Therapeutic Strategy against Parkinson's Disease

2003 • 159 citations

Problems with long-term levodopa therapy for Parkinson's disease.

1994 • 157 citations

Role of α-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice

2003 • 142 citations

Sensitivity to MPTP is not increased in Parkinson's disease‐associated mutant α‐synuclein transgenic mice

2001 • 127 citations

Mitochondria1 respiratory chain activity in skeletal muscle from patients with Parkinson's disease

1993 • 127 citations

Phosphorylation of α-synuclein characteristic of synucleinopathy lesions is recapitulated in α-synuclein transgenic Drosophila

2003 • 121 citations

Interaction of α‐Phenyl‐N‐tert‐Butyl Nitrone and Alternative Electron Acceptors with Complex I Indicates a Substrate Reduction Site Upstream from the Rotenone Binding Site

1998 • 118 citations

Physiology and Pathophysiology of α‐Synuclein: Cell Culture and Transgenic Animal Models Based on a Parkinson's Disease‐associated Protein

2000 • 108 citations

Amino acid determinants of α‐synuclein aggregation: putting together pieces of the puzzle

2002 • 105 citations

α-Synuclein Inclusions in Amygdala in the Brains of Patients with the Parkinsonism-Dementia Complex of Guam

2000 • 99 citations

?-Synuclein expression in substantia nigra and cortex in Parkinson's disease

1999 • 98 citations

Neuron-specific transgene expression of Bcl-XL but not Bcl-2 genes reduced lesion size after permanent middle cerebral artery occlusion in mice

1999 • 97 citations

Clinical and neuropathological correlates of Lewy body disease

2003 • 91 citations

α-synuclein fibrils constitute the central core of oligodendroglial inclusion filaments in multiple system atrophy

2003 • 82 citations

Indices of oxidative stress in Parkinson’s disease, Alzheimer’s disease and dementia with Lewy bodies

1997 • 61 citations

Electron microscopy of Lewy bodies in the amygdala-parahippocampal region. Comparison with inclusion bodies in the MPTP-treated squirrel monkey.

1996 • 54 citations

Localization of α-, β-, and γ-synuclein during neuronal development and alterations associated with the neuronal response to axonal trauma

2003 • 39 citations

Enhanced oligomerization of the alpha-synuclein mutant by the Cu,Zn-superoxide dismutase and hydrogen peroxide system.

2003 • 39 citations

The ceruloplasmin and hydrogen peroxide system induces α-synuclein aggregation in vitro

2002 • 36 citations

Enhanced Oligomerization of the α-Synuclein Mutant by the Cu,Zn-Superoxide Dismutase and Hydrogen Peroxide System

2003 • 34 citations

Implications for Pathogenesis and Therapy

1996 • 20 citations

Engineered modeling and the secrets of Parkinson's disease

2001 • 19 citations

Chairmanʼs Conclusion

1994 • 17 citations