Hypothesis: Proteasomal Dysfunction

Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly

1996 • 5,498 citations

Translating cell biology into therapeutic advances in Alzheimer's disease

1999 • 1,592 citations

Oxidative Damage Linked to Neurodegeneration by Selective α-Synuclein Nitration in Synucleinopathy Lesions

2000 • 1,526 citations

Role of Free Radicals in the Neurodegenerative Diseases

2001 • 1,490 citations

Triggering and modulation of apoptosis by oxidative stress

2000 • 1,315 citations

Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease.

1991 • 1,290 citations

4‐Hydroxynonenal‐Derived Advanced Lipid Peroxidation End Products Are Increased in Alzheimer's Disease

1997 • 1,018 citations

Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease.

1996 • 976 citations

Degradation of oxidized proteins in mammalian cells

1997 • 845 citations

Endogenous nitric oxide synthesis: Biological functions and pathophysiology

1999 • 796 citations

Impaired Proteasome Function in Alzheimer's Disease

2000 • 795 citations

Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis

1997 • 792 citations

A Role for 4‐Hydroxynonenal, an Aldehydic Product of Lipid Peroxidation, in Disruption of Ion Homeostasis and Neuronal Death Induced by Amyloid β‐Peptide

1997 • 779 citations

Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone.

1991 • 734 citations

Evidence that 4-Hydroxynonenal Mediates Oxidative Stress-Induced Neuronal Apoptosis

1997 • 727 citations

Proteasomal function is impaired in substantia nigra in Parkinson's disease

2001 • 631 citations

Formation of high molecular weight complexes of mutant Cu,Zn-superoxide dismutase in a mouse model for familial amyotrophic lateral sclerosis

2000 • 604 citations

Evidence of neuronal oxidative damage in Alzheimer's disease.

1996 • 602 citations

Protein Nitration in Parkinsonʼs Disease

1998 • 551 citations

The Proteasome, a Novel Protease Regulated by Multiple Mechanisms

1999 • 540 citations

In Situ Oxidative Catalysis by Neurofibrillary Tangles and Senile Plaques in Alzheimer’s Disease

2000 • 526 citations

An Assessment of Oxidative Damage to Proteins, Lipids, and DNA in Brain from Patients with Alzheimer's Disease

1997 • 526 citations

Electrochemical Analysis of Protein Nitrotyrosine and Dityrosine in the Alzheimer Brain Indicates Region-Specific Accumulation

1998 • 507 citations

Tyrosine nitration: Localisation, quantification, consequences for protein function and signal transduction

2001 • 504 citations

Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain.

1996 • 493 citations

Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis

2001 • 490 citations

Bcl-2: Prolonging Life in a Transgenic Mouse Model of Familial Amyotrophic Lateral Sclerosis

1997 • 482 citations

Lactacystin, Proteasome Function, and Cell Fate

1998 • 420 citations

Degradation of α-Synuclein by Proteasome

1999 • 406 citations

Increased Caspase 3 and Bax Immunoreactivity Accompany Nuclear GAPDH Translocation and Neuronal Apoptosis in Parkinson's Disease

2000 • 402 citations

Advanced Glycation End Products in Alzheimer's Disease and Other Neurodegenerative Diseases

1998 • 389 citations

Protein modification by the lipid peroxidation product 4‐hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients

1998 • 382 citations

Caspase-1 and -3 are sequentially activated in motor neuron death in Cu,Zn superoxide dismutase-mediated familial amyotrophic lateral sclerosis

2000 • 346 citations

Increased 8,12-iso-iPF2?-VI in Alzheimer's disease: Correlation of a noninvasive index of lipid peroxidation with disease severity

2000 • 345 citations

Clinical, biochemical and molecular genetic correlations in Friedreich's ataxia

2000 • 333 citations

4-Hydroxy-2-nonenal-mediated Impairment of Intracellular Proteolysis during Oxidative Stress

1999 • 320 citations

Oxidative stress in patients with Friedreich ataxia

2000 • 307 citations

Proteasome Inhibitors Activate Stress Kinases and Induce Hsp72

1998 • 304 citations

Neuroprotective strategies for basal ganglia degeneration: Parkinson's and Huntington's diseases

2000 • 298 citations

Effect of Age and Caloric Intake on Protein Oxidation in Different Brain Regions and on Behavioral Functions of the Mouse

1996 • 290 citations

Decreased levels of proteasome activity and proteasome expression in aging spinal cord

2000 • 288 citations

Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant

1997 • 287 citations

An activity in rat tissues that modifies nitrotyrosine-containing proteins

1998 • 278 citations

Nitric oxide and peroxynitrite. The ugly, the uglier and the not so good

1999 • 273 citations

Inhibitors of the proteasome pathway interfere with induction of nitric oxide synthase in macrophages by blocking activation of transcription factor NF-kappa B.

1996 • 265 citations

Inhibition of the multicatalytic proteinase (proteasome) by 4‐hydroxy‐2‐nonenal cross‐linked protein

1997 • 264 citations

Possible involvement of proteasome inhibition in aging: implications for oxidative stress

2000 • 264 citations

Neuronal cell death in nervous system development, disease, and injury (Review)

2001 • 256 citations

Peroxynitrite Increases the Degradation of Aconitase and Other Cellular Proteins by Proteasome

1998 • 254 citations

Increased CSF F ₂ -isoprostane concentration in probable AD

1999 • 250 citations

Poly-ADP ribose polymerase activates nuclear proteasome to degrade oxidatively damaged histones

1999 • 228 citations

Effect of the overexpression of wild‐type or mutant α‐synuclein on cell susceptibility to insult

2001 • 227 citations

Oxidative Stress and Motor Neurone Disease

1999 • 220 citations

Roles of Lipid Peroxidation in Modulation of Cellular Signaling Pathways, Cell Dysfunction, and Death in the Nervous System

1998 • 216 citations

Immunocytochemical Co-localization of the Proteasome in Ubiquitinated Structures in Neurodegenerative Diseases and the Elderly

1997 • 214 citations

In Alzheimer's Disease, Heme Oxygenase Is Coincident with Alz50, an Epitope of τ Induced by 4‐Hydroxy‐2‐Nonenal Modification

2000 • 202 citations

Neurotoxic Aβ peptides increase oxidative stress in vivo through NMDA‐receptor and nitric‐oxide‐synthase mechanisms, and inhibit complex IV activity and induce a mitochondrial permeability transition in vitro

2001 • 199 citations

Remarkable increase in cerebrospinal fluid 3-nitrotyrosine in patients with sporadic amyotrophic lateral sclerosis

1999 • 189 citations

Phorbol Esters Increase Dopamine Transporter Phosphorylation and Decrease Transport V_max

1997 • 187 citations

Neuronal DNA damage precedes tangle formation and is associated with up-regulation of nitrotyrosine in Alzheimer's disease brain

1997 • 175 citations

The role of mitochondrial dysfunction and neuronal nitric oxide in animal models of neurodegenerative diseases

1997 • 174 citations

Protein precipitation: a common etiology in neurodegenerative disorders?

1998 • 158 citations

Distribution of Reducible 4-Hydroxynonenal Adduct Immunoreactivity in Alzheimer Disease is Associated with APOE Genotype

1998 • 154 citations

Monoclonal Antibodies for Detection of 4-Hydroxynonenal Modified Proteins

1996 • 152 citations

Recent advances in the molecular pathogenesis of Friedreich ataxia

2000 • 148 citations

Untitled

1997 • 146 citations

4-Hydroxynonenal-modified amyloid-β peptide inhibits the proteasome: possible importance in Alzheimer’s disease*

2000 • 140 citations

Alpha-synuclein immunoisolation of glial inclusions from multiple system atrophy brain tissue reveals multiprotein components.

1999 • 140 citations

Effect of proteasome inhibition on cellular oxidative damage, antioxidant defences and nitric oxide production

2001 • 136 citations

4-Hydroxynonenal, a Product of Lipid Peroxidation, Damages Cholinergic Neurons and Impairs Visuospatial Memory in Rats

1998 • 133 citations

Proteasome Inhibition in Neuronal Cells Induces a Proinflammatory Response Manifested by Upregulation of Cyclooxygenase-2, Its Accumulation as Ubiquitin Conjugates, and Production of the Prostaglandin PGE2

2000 • 129 citations

Activation of the Cell Death Program by Nitric Oxide Involves Inhibition of the Proteasome

1999 • 127 citations

Age-related changes in the 20S and 26S proteasome activities in the liver of male F344 rats

1998 • 125 citations

The Magnitude of Brain Lipid Peroxidation Correlates with the Extent of Degeneration but Not with Density of Neuritic Plaques or Neurofibrillary Tangles or with APOE Genotype in Alzheimer's Disease Patients

1999 • 118 citations

α‐Synuclein Immunoisolation of Glial Inclusions from Multiple System Atrophy Brain Tissue Reveals Multiprotein Components

1999 • 115 citations

Effect of overexpression of Bcl-2 on cellular oxidative damage, nitric oxide production, antioxidant defenses, and the proteasome

2001 • 110 citations

Bioenergetics in Huntington's Disease

1999 • 103 citations

Role of protein-bound carbonyl groups in the formation of advanced glycation endproducts

1997 • 101 citations

Decreased Proteasome-Mediated Degradation in T Cells from the Elderly: A Role in Immune Senescence

1999 • 98 citations

Molecular Biology of the Proteasome

1998 • 98 citations

Role of the proteasome in Alzheimer’s disease

2000 • 95 citations

Proteasome Inhibitor‐Induced Apoptosis of Glioma Cells Involves the Processing of Multiple Caspases and Cytochrome c Release

2000 • 93 citations

Proteasomal dysfunction induced by 4‐hydroxy‐2,3‐trans‐nonenal, an end‐product of lipid peroxidation: a mechanism contributing to neurodegeneration?

2002 • 92 citations

Mitochondrial Nitric Oxide Synthase, Oxidative Stress and Apoptosis

2001 • 89 citations

Lack of involvement of neuronal nitric oxide synthase in the pathogenesis of a transgenic mouse model of familial amyotrophic lateral sclerosis

1999 • 86 citations

Lactacystin, a specific inhibitor of the proteasome, induces apoptosis and activates caspase-3 in cultured cerebellar granule cells

2000 • 86 citations

Effect of overexpression of wild‐type and mutant Cu/Zn‐superoxide dismutases on oxidative stress and cell death induced by hydrogen peroxide, 4‐hydroxynonenal or serum deprivation: potentiation of injury by ALS‐related mutant superoxide dismutases and protection by Bcl‐2

2001 • 81 citations

Inhibition versus induction of apoptosis by proteasome inhibitors depends on concentration

1998 • 77 citations

Aggregation of ubiquitin and a mutant ALS-linked SOD1 protein correlate with disease progression and fragmentation of the Golgi apparatus

2000 • 71 citations

The Role of Nitric Oxide in Neurodegeneration

1998 • 70 citations

Alpha-synuclein immunoreactivity of huntingtin polyglutamine aggregates in striatum and cortex of Huntington's disease patients and transgenic mouse models

2000 • 66 citations

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

1997 • 61 citations

Parkin is metabolized by the ubiquitin/proteosome system

2000 • 56 citations

Proteasome inhibition results in increased poly-ADP-ribosylation: Implications for neuron death

2000 • 53 citations

No Evidence for Increased Oxidative Damage to Lipids, Proteins, or DNA in Huntington's Disease

2000 • 49 citations

Neuroprotection achieved with a novel proteasome inhibitor which blocks NF-κB activation

2000 • 48 citations

Properties of the Nuclear Proteasome Activator PA28γ (REGγ)

2000 • 45 citations

Mutant CuZn superoxide dismutase in motor neuron disease

1998 • 43 citations

A New Structural Class of Proteasome Inhibitors that Prevent NF-κB Activation

1998 • 39 citations

Hemoglobin and iron-evoked oxidative stress in the brain: Protection by bile pigments, managanese andS-nitrosoglutathione

1999 • 39 citations

Inhibitory and Stimulatory Effects of Lactacystin on Expression of Nitric Oxide Synthase Type 2 in Brain Glial Cells

2000 • 37 citations

Does failure of parkin-mediated ubiquitination cause juvenile parkinsonism?

2000 • 34 citations

Plaque-Associated Neuronal Proteins: A Recurrent Motif in Neuritic Amyloid Deposits throughout Diverse Cortical Areas of the Alzheimer's Disease Brain

1994 • 30 citations

Gain in functions of mutant Cu,Zn-superoxide dismutases as a causative factor in familial amyotrophic lateral sclerosis: Less reactive oxidant formation but high spontaneous aggregation and precipitation

2000 • 27 citations

Role of Nitric Oxide in the Control of Mitochondrial Function

1999 • 27 citations

Anti-inflammatory substances – a new therapeutic option in Alzheimer's disease

1999 • 26 citations

Pharmacological proteasome inhibitors and their therapeutic potential

2000 • 24 citations

Transplantation of irides or sensory ganglia to the anterior eye chamber of the rat: Survival and sprouting of substance P-containing neurones

1982 • 8 citations

The effects of various agents upon the sensitivity of Staphylococcus aureus to penicillin.

1947 • 7 citations

Common mechanisms of oxidative damage in chronic neurodegenerative conditions: potential points of therapeutic intervention

1999 • 6 citations

Capturing the sublimity of a free radical gas

1999 • 2 citations