尼古丁与帕金森病的神经保护-猫眼课题宝

尼古丁与帕金森病的神经保护

批准号：

7779434

负责人：

JAYARAMAN RAO

金额：

$7.12万

依托单位：

OCHSNER CLINIC FOUNDATION

依托单位国家：

美国

项目类别：

财政年份：

2002

资助国家：

美国

项目状态：

已结题

起止时间：

2002-09-30 至 2013-11-30

来源：

https://reporter.nih.gov/project-details/7779434

关键词：

1-Methyl-4-phenylpyridinium Abbreviations Acute Adopted Affinity Amyloid Animal Model Animals Apoptosis Apoptosis Inhibitor Apoptotic BCL2L11 gene Basal Ganglia Bax protein Binding Blood Boxing Brain Bungarotoxins Caring Caspase Caspase-1 Cell Culture Techniques Cell Death Cell Line Cell Survival Cells Cerebral cortex Cessation of life Cholinergic Receptors Chronic Conduct Clinical Trials Continuous Infusion Corpus striatum structure Cyclic AMP Cyclic AMP Response Element DNA Disease Disease Progression Docking Dopamine Dose Dropout Drug Kinetics Elements Embryo Epidemiologic Studies Etiology Experimental Models FGF2 gene Fibroblast Growth Factor 2 Fos-Related Antigens Functional disorder Gated Ion Channel Genes Glutamates Goals Hippocampus (Brain)Human Hypoglycemia Implant In Situ Nick-End Labeling Incidence Inhalators Injection of therapeutic agent Ischemia Knock-out Laboratories Learning Life Ligands Longevity MAP Kinase Kinase 2 Mediating Medical Memory Messenger RNA Methamphetamine Methods Mitogen Activated Protein Kinase 1 Modeling Molecular Monkeys Mus NF-kappa B NGFR Protein Neurodegenerative Disorders Neurons Neuroprotective Agents Nicotine Nicotine Dependence Nicotinic Receptors Nose Operative Surgical Procedures Oral Oxidopamine PC12 Cells Parkinson Disease Pathway interactions Patients Pattern Pharmaceutical Preparations Pharmacodynamics Phenotype Phosphorylation Phosphotransferases Play Preparation Principal Investigator Protein Kinase Protein Tyrosine Kinase Proteins Proto-Oncogene Proteins c-akt Quality of life Rattus Receptor Protein-Tyrosine Kinases Recombinants Research Research Personnel Resistance Rodent Role Route Schedule Septal Nuclei Signal Transduction Smoking Solutions Substantia nigra structure TP53 gene Thalamic structure Therapeutic Agents Time Toxic effect Tumor Necrosis Factor Ligand Superfamily Member 6 YOYO-1 addiction alpha Bungarotoxin annexin A5 caspase-3 caspase-8 cost density dopaminergic neuron erythroidine immunoreactivity improved in vivo inhibitor/antagonist intraperitoneal intravenous injection mutant neuronal cell body neuronal survival neuroprotection neurotoxicity neurotrophic factor nicotine patch nicotine replacement nicotinic receptor beta2 overexpression prevent pro-apoptotic protein programs receptor subcutaneous young adult

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DESCRIPTION (provided by applicant): Parkinson's disease (PD) is progressive neurodegenerative disorder. A combination of medical and surgical treatments has improved the quality of the lives of most PD patients. But the relentless progression of degeneration of the substantial nigra and consequent loss of dopamine in the basal ganglia ultimately leads to a severe debilitating state. Efforts to slow the disease even to a small degree will extend the life span and improve the quality of a patient's life and reduce the national burden of cost of care of PD patients.At present there are no drugs that can slow the progression of the disease. In this proposal it is hypothesized, that among all the available compounds, nicotine shows significant promise to be a neuroprotective agent for the degenerating dopaminergic neurons in PD. We will discuss evidence to support that: 1. Nicotine is neuroprotective in several models of neurotoxicity, 2. The neuroprotective effects of nicotine are mediated via several well established cell survival and anti-apoptotic molecular cascades, 3. The degenerating dopaminergic neurons in PD do show evidence of apoptotic death, 4. Nicotine is neuroprotective in animal models of PD, and 5. Nicotine's neuroprotective actions are accomplished by the activation of P13K/Akt antiapoptotic pathways by alpha4 - beta2 and aIpha7 - beta2 nicotinic receptors, which are abundant in the substantial nigra and striatum. A tentative research plan to conduct clinical trial using Transdermal nicotine patches is also proposed.

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