BLR&D Research Career Scientist Application

BLR

• 批准号: 10047235
• 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/10047235
• 关键词: Address; Alzheimer' s Disease; Alzheimer' s disease pathology; Animal Model; Apoptosis; Aspirin; Astrocytes; Attenuated; Autoimmune; Binding; Biogenesis; Brain; Brain region; CNS Demyelinating Autoimmune Diseases; CNS autoimmune disease; Cell Death; Cells; Cellular Metabolic Process; Cessation of life; Chemicals; Cholesterol; Clinical Trials; Dementia; Demyelinations; Disease; Exhibits; Exposure to; Fatty acid glycerol esters; Gender; Gliosis; Health; Hippocampus (Brain); Human; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Inflammation; Integrins; Interferon Type II; Interleukin-12; Knowledge; Lead; Lesion; Ligands; Link; Lovastatin; Magnetic Resonance Imaging; Mediating; Memory; Microglia; Multiple Sclerosis; Mus; Myelin; Nature; Nerve Degeneration; Neuraxis; 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; 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）]是一组神经退行性疾病。 由大脑不同区域的神经元进行性死亡引起的毁灭性疾病。对 另一方面，多发性硬化（MS）是最常见的中枢神经系统自身免疫性疾病 系统，导致少突胶质细胞死亡和脱髓鞘。我们的实验室主要研究中枢神经系统 在帕金森病（PD）和阿尔茨海默病中导致神经元死亡的中枢神经系统（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 CNS神经胶质细胞（星形胶质细胞和小胶质细胞）的活化，不同的促炎因子的过度产生， 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 角，我们一直在研究神经胶质细胞被激活释放不同的机制， 用于诱导神经元中的细胞凋亡和细胞死亡的促炎分子和神经毒素， 少突胶质细胞我们还参与了识别神经胶质细胞可能通过的信号通路的研究。 重新定向以产生神经保护分子，神经干细胞可以被驱动向神经元， 神经退行性CNS内的髓鞘生成细胞（少突胶质细胞）。最后，我们试图 在不同动物中抑制神经毒性信号传导途径和/或增强神经保护性信号传导途径 通过无毒药物建立神经退行性疾病模型，以达到神经保护作用。由于许多 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