A5085303733- Parkinson's Disease Mechanisms and Treatments
- Genetics, Aging, and Longevity in Model Organisms
- Alzheimer's disease research and treatments
- Nerve injury and regeneration
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Nuclear Receptors and Signaling
- Autophagy in Disease and Therapy
- Neurological diseases and metabolism
- Sulfur Compounds in Biology
- Neuroinflammation and Neurodegeneration Mechanisms
- Telomeres, Telomerase, and Senescence
- RNA regulation and disease
- Genetic Neurodegenerative Diseases
- Virus-based gene therapy research
- Tryptophan and brain disorders
- Neurological disorders and treatments
- Iron Metabolism and Disorders
- Paraquat toxicity studies and treatments
- Pluripotent Stem Cells Research
- Redox biology and oxidative stress
- Trace Elements in Health
- Pomegranate: compositions and health benefits
- Cholinesterase and Neurodegenerative Diseases
- Circadian rhythm and melatonin
Buck Institute for Research on Aging
2016-2025
University of Southern California
2000-2024
Marin Community Foundation
2014-2023
Roche (Switzerland)
2017
Evotec (Germany)
2017
University of Puerto Rico, Medical Sciences Campus
2010
San Jose State University
2006
Massachusetts General Hospital
1991-2002
Brigham Young University
2000
The Pirbright Institute
1999
Glutathione peroxidase (GSHPx) is a critical intracellular enzyme involved in detoxification of hydrogen peroxide (H(2)O(2)) to water. In the present study we examined susceptibility mice with disruption glutathione gene neurotoxic effects malonate, 3-nitropropionic acid (3-NP), and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). knock-out showed no evidence neuropathological or behavioral abnormalities at 2-3 months age. Intrastriatal injections malonate resulted significant twofold...
Exposure to the herbicide paraquat (PQ) is associated with an increased risk of idiopathic Parkinson's disease (PD). Therapies based on PQ's presumed mechanisms action have not, however, yielded effective therapies. Cellular senescence anticancer mechanism that arrests proliferation replication-competent cells and results in a pro-inflammatory senescence-associated secretory phenotype (SASP) capable damaging neighboring tissues. Here, we demonstrate senescent cell markers are preferentially...
Aging is associated with changes in circulating levels of various molecules, some which remain undefined. We find that concentrations taurine decline aging mice, monkeys, and humans. A reversal this through supplementation increased the health span (the period healthy living) life mice monkeys. Mechanistically, reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, attenuated inflammaging. In humans, lower correlated...
Parkinson's disease (PD) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity are both associated with dopaminergic neuron death in the substantia nigra (SN). Apoptosis has been implicated this cell loss; however, whether or not it is a major component of pathology remains controversial. Caspases class proteases involved apoptotic process. To evaluate role caspases PD, we analyzed caspase activation MPTP-treated mice, cultured cells, postmortem PD brain tissue. MPTP was found to...
Abstract Systemic treatment of mice with the herbicide paraquat causes selective loss nigrostriatal dopaminergic neurons, reproducing primary neurodegenerative feature Parkinson's disease. To elucidate role oxidative damage in neurotoxicity, time‐course neurodegeneration was correlated to changes 4‐hydroxy‐2‐nonenal (4‐HNE), a lipid peroxidation marker. When were exposed three weekly injections paraquat, no nigral cell observed after first administration, whereas significant reduction...
Age-related increases in monoamine oxidase B (MAO-B) may contribute to neurodegeneration associated with Parkinson's disease (PD). The MAO-B inhibitor deprenyl, a long-standing antiparkinsonian therapy, is currently used clinically concert the dopamine precursor L-DOPA. Clinical studies suggesting that deprenyl treatment alone not protective against PD mortality were targeted symptomatic patients. However, loss at least 60% by time symptomatically detectable, therefore lack of effect...
Oxidative stress appears to play an important role in degeneration of dopaminergic neurons the substantia nigra (SN) associated with Parkinson's disease (PD). The SN early PD patients have dramatically decreased levels thiol tripeptide glutathione (GSH). GSH plays multiple roles nervous system both as antioxidant and a redox modulator. We generated PC12 cell lines which can be inducibly down-regulated via doxycycline induction antisense messages against heavy light subunits...
Environmental exposure to the oxidant-producing herbicide paraquat has been implicated as a risk factor in Parkinson's disease. Although intraperitoneal injections mice cause selective loss of dopaminergic neurons substantia nigra pars compacta, exact mechanism involved is still poorly understood. Our data show that induces sequential phosphorylation c-Jun N-terminal kinase (JNK) and activation caspase-3 neuronal death both vitro vivo. These effects are diminished by specific JNK inhibitor...
Aging is a three-stage process: metabolism, damage, and pathology. The biochemical processes that sustain life generate toxins as an intrinsic side effect. These cause of which small proportion cannot be removed by any endogenous repair process thus accumulates. This accumulating damage ultimately drives age-related degeneration. Interventions can designed at all three stages. However, intervention in metabolism only modestly postpone pathology, because production so property metabolic...
Following its activation by PINK1, parkin is recruited to depolarized mitochondria where it ubiquitinates outer mitochondrial membrane proteins, initiating lysosomal-mediated degradation of these organelles. Mutations in the gene encoding parkin, PARK2, result both familial and sporadic forms Parkinson's disease (PD) conjunction with reductions removal damaged mitochondria. In contrast what has been reported for other PARK2 mutations, expression Q311X mutation vivo mice appears involve a...