The Role SVOP in Neurotransmission

SVOP 在神经传递中的作用

• 批准号: 7892915
• 负责人: Sandra M Bajjalieh
• 金额: $ 7.8万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-15 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7892915
• 关键词: Affect; Antiepileptic Agents; Binding; Binding Sites; Botulinum Toxins; Brain; Breeding; Cells; Development; Drug Delivery Systems; Dyskinetic syndrome; Enterobacteria phage P1 Cre recombinase; Epilepsy; Event; Excision; Exons; FDA approved; FLP recombinase; Family; Generations; Genes; Genetic Recombination; Genetic Transcription; Goals; Introns; Knockout Mice; Knowledge; Levetiracetam; Mediating; Molecular; Motivation; Mus; Neomycin resistance gene; Nervous System Physiology; Neurons; Pharmaceutical Preparations; Phenotype; Pilot Projects; Play; Proteins; Reagent; Role; Site; Synapses; Synaptic Vesicles; Testing; Tetanus; Therapeutic Intervention; Tissues; base; nervous system disorder; neuromuscular disorder therapy; neurotransmission; neurotransmitter release; novel therapeutics; painful neuropathy; presynaptic; public health relevance; research study; therapeutic target

DESCRIPTION (provided by applicant): The precise control of neurotransmitter release is mediated by proteins specific to synapses. One family of essential regulators is SV2, a family of transporter-like proteins that have emerged as a target of new therapies to treat nervous system disorders. Synaptic vesicles also contain a related protein, SVOP (SV2-like protein), about which very little is known. To study the role of SVOP in neurotransmission, we propose to establish mouse lines in which SVOP expression can be universally or selectively disrupted. These mice will be a crucial reagent in determining both how SVOP contributes to neuronal functioning and whether it holds promise in the development of new therapeutics. PUBLIC HEALTH RELEVANCE: This pilot project will generate a genetically modified mouse line that will be used to identify the function of SVOP, a transporter-like protein present on synaptic vesicles about which very little is known. SVOP has significant similarity to SV2, a small family of synaptic vesicle proteins that are essential regulators of neurotransmitter release. SV2A is the binding site of a new class of antiepileptic drugs that are also finding use in the treatment of other nervous system disorders including neuropathic pain and dyskinesias. The proposed mouse line will play a crucial role in vetting SVOP's potential as an alternate drug target.

描述（由申请人提供）：神经递质释放的精确控制由突触特异性蛋白介导。一个重要的调节因子家族是SV2，这是一个转运蛋白样蛋白家族，已成为治疗神经系统疾病的新疗法的靶点。突触囊泡还含有一种相关的蛋白质，SVOP（SV2样蛋白），对此知之甚少。为了研究SVOP在神经传递中的作用，我们建议建立SVOP表达可以被普遍或选择性破坏的小鼠品系。这些小鼠将是确定SVOP如何促进神经元功能以及它是否有希望开发新疗法的关键试剂。 公共卫生相关性：这个试点项目将产生一个转基因小鼠系，将用于识别SVOP的功能，SVOP是一种存在于突触囊泡上的转运蛋白样蛋白，对此知之甚少。SVOP与SV2具有显著的相似性，SV2是突触囊泡蛋白的一个小家族，是神经递质释放的重要调节剂。SV2A是一类新型抗癫痫药物的结合位点，这些药物也可用于治疗其他神经系统疾病，包括神经性疼痛和运动障碍。拟议的小鼠品系将在审查SVOP作为替代药物靶点的潜力方面发挥关键作用。