Neuroprotection in MS: A Cell-Specific and Region-Specific Transcriptomics Approach

MS 中的神经保护：细胞特异性和区域特异性转录组学方法

• 批准号: 10403989
• 负责人: RHONDA R VOSKUHL
• 金额: $ 44.46万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10403989
• 关键词: Address; Adult; Affect; Astrocytes; Autopsy; Cells; Cognition; Disease; Experimental Autoimmune Encephalomyelitis; Gene Expression; Hippocampus (Brain); Human; Modeling; Molecular; Multiple Sclerosis; Nerve Degeneration; Neurologic; Neurons; Oligodendroglia; Optic Nerve; Pathway interactions; Patients; Pre-Clinical Model; Public Health; Spinal Cord; Tissues; Translating; Vision; Vision Disorders; Walking; cognitive disability; disability; improved; middle age; multiple sclerosis patient; neuroprotection; novel; remyelination; transcriptome; transcriptomics

This proposal will use a cell-specific and region-specific transcriptomics approach in the MS preclinical model to reveal new candidate targets for a tailored, disability-specific, neuroprotective treatment approach in MS. Neurological pathways underling walking, vision, and cognition differ, as do the cells and molecules within the neuroanatomic regions that serve them. MS patients are heterogeneous with regard to which disability is the most severely affected. Thus, we hypothesize that a one size fits all neuroprotective treatment for all disabilities in MS may not be possible. Rather, a disability specific discovery approach is needed. Aim #1. Identify neurodegenerative mechanisms using the region-specific astrocyte transcriptome in EAE, here focusing beyond spinal cord, on optic nerve and hippocampus. Aim #2. Identify neurodegenerative mechanisms using the region-specific neuronal transcriptome in EAE. Aim #3. Use region-specific oligodendrocyte transcriptomics to determine molecular mechanisms of remyelination in two complementary MS models. Aim #4. To begin to translate findings to MS, we will determine whether the alteration in gene expression in key pathways in MS models occurs in MS using human autopsy tissues. Together, this proposal will reveal distinct cell-specific and region-specific mechanisms underlying walking, vision, and cognitive disability in MS.

该建议将在MS临床前模型中使用细胞特异性和区域特异性转录组学方法

项目成果

Decreased neurofilament light chain levels in estriol-treated multiple sclerosis.

• DOI: 10.1002/acn3.51622
• 发表时间: 2022-08
• 期刊: Annals of clinical and translational neurology
• 影响因子: 5.3