BLR&D Research Career Scientist Application

BLR

基本信息

批准号：
10515296
负责人：
KALIPADA PAHAN
金额：
--
依托单位：
JESSE BROWN VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-10-01 至 2024-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10515296
关键词：
Address Alzheimer&apos s Disease Alzheimer&apos s disease pathology Animal Model Aspirin Astrocytes Attenuated Autoimmune Binding Biogenesis Brain Brain region CNS Demyelinating Autoimmune Diseases CNS autoimmune disease Cell Death Cells Cellular Metabolic Process Central Nervous System Cessation of life Chemicals Cholesterol Clinical Trials Dementia Demyelinations Disease Exhibits Exposure to Fatty acid glycerol esters Gender Gliosis Health Hippocampus Human Hydroxymethylglutaryl-CoA Reductase Inhibitors Incidence Induction of Apoptosis Inflammation Inflammatory Integrins Interferon Type II Interleukin-12 Investments Knowledge acquisition Lesion Ligands Link Lovastatin Magnetic Resonance Imaging Mediating Memory Microglia Multiple Sclerosis Mus Myelin Nature Nerve Degeneration Neurodegenerative Disorders Neuroglia Neurology Neurons Neurotoxins Nitric Oxide Oligodendroglia PPAR alpha Parkinson Disease Pathway interactions Pharmaceutical Preparations Poison Process Production Proteolysis Recovery of Function Regulation Regulatory T-Lymphocyte Research Risk Safety Scientist Services Signal Pathway Signal Transduction T-Lymphocyte TLR2 gene Therapeutic Therapeutic Agents Time Veterans Vietnamese War agent orange brain cell career combat improved monomer nerve stem cell neuroinflammation neuron apoptosis neuron loss neuroprotection neurotoxic neurotrophic factor prostate cancer cell

项目摘要

Neurodegenerative disorders [e.g. Alzheimer's disease (AD) and Parkinson's disease (PD)] are a group of devastating conditions that are caused by progressive death of neurons in different regions of the brain. On the other hand, multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system, resulting in oligodendrocytes death and demyelination. Our lab primarily focuses on central nervous system (CNS) cell signaling that leads to neuronal death in Parkinson's disease (PD) and Alzheimer's disease (AD) and demyelination in multiple sclerosis (MS). All these disorders are characterized by activation of CNS glial cells (astroglia and microglia), excessive production of different proinflammatory molecules within the CNS, and death of either oligodendroglia (MS) or neurons (AD and PD). From several angles, we have been investigating mechanisms by which glial cells are activated to release different proinflammatory molecules and neurotoxins for inducing apoptosis and cell death in neurons and oligodendroglia. We are also involved in identifying signaling pathways by which glial cells may be redirected to produce neuroprotective molecules and neural stem cells could be driven towards neurons and myelin-producing cells (oligodendrocytes) within the neurodegenerative CNS. Finally, we are trying to suppress neurotoxic signaling pathways and/or boost neuroprotective signaling pathways in different animal models of neurodegenerative diseases by nontoxic drugs in order to achieve neuroprotection. Since many veterans are suffering from dementia, AD, PD, and MS, results from these studies will directly help veterans. 1

神经退行性疾病[例如阿尔茨海默氏病（AD）和帕金森氏病（PD）是一组由大脑不同区域的神经元进行性死亡引起的毁灭性疾病。在另一方面，多发性硬化症（MS）是中枢神经中最常见的自身免疫性疾病系统，导致少突胶质细胞死亡和脱髓鞘。我们的实验室主要关注中枢神经导致帕金森氏病（PD）和阿尔茨海默氏病神经元死亡的系统（CNS）信号传导多发性硬化症（MS）中的疾病（AD）和脱髓鞘。所有这些疾病的特征是 CNS神经胶质细胞（星形胶质细胞和小胶质细胞）的激活，不同促炎的过度产生中枢神经系统内的分子，以及寡头（MS）或神经元（AD和PD）的死亡。来自几个角度，我们一直在研究激活神经胶质细胞以释放不同的机制促炎分子和神经毒素，用于诱导神经元的细胞凋亡和细胞死亡和细胞死亡寡头。我们还参与了识别神经胶质细胞可能为的信号通路重定向以产生神经保护分子和神经干细胞，可以驱动到神经元和神经退行性CNS中产生髓磷脂的细胞（少突胶质细胞）。最后，我们正在尝试抑制神经毒性信号通路和/或增加不同动物中神经保护信号通路通过无毒药物的神经退行性疾病模型，以实现神经保护。自从很多退伍军人患有痴呆症，AD，PD和MS，这些研究的结果将直接帮助退伍军人。 1