BLR&D Research Career Scientist Application

BLR

• 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
• 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' s Disease; Alzheimer' 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

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 [例如阿尔茨海默病 (AD) 和帕金森病 (PD)] 是一组 由大脑不同区域的神经元逐渐死亡引起的破坏性病症。在 另一方面，多发性硬化症（MS）是最常见的中枢神经自身免疫性疾病 系统，导致少突胶质细胞死亡和脱髓鞘。我们的实验室主要专注于中枢神经 导致帕金森病 (PD) 和阿尔茨海默病神经元死亡的系统 (CNS) 细胞信号传导 疾病（AD）和多发性硬化症（MS）中的脱髓鞘。所有这些疾病的特点是 中枢神经系统胶质细胞（星形胶质细胞和小胶质细胞）的激活，不同促炎物质的过度产生 CNS 内的分子，以及少突胶质细胞 (MS) 或神经元（AD 和 PD）的死亡。从几个 从角度来看，我们一直在研究神经胶质细胞被激活释放不同物质的机制 促炎分子和神经毒素，用于诱导神经元和细胞凋亡和细胞死亡 少突胶质细胞。我们还参与鉴定神经胶质细胞可能通过的信号通路 重定向以产生神经保护分子，神经干细胞可以被驱动到神经元和 神经退行性中枢神经系统内产生髓磷脂的细胞（少突胶质细胞）。最后，我们正在努力 抑制不同动物的神经毒性信号通路和/或增强神经保护信号通路 通过无毒药物建立神经退行性疾病模型，以实现神经保护。由于许多 退伍军人患有痴呆症、阿尔茨海默病、帕金森病和多发性硬化症，这些研究的结果将直接帮助退伍军人。 1