Non-apoptotic caspase activity in neurons

神经元中的非凋亡 caspase 活性

• 批准号: 9093400
• 负责人: J. Marie Hardwick
• 金额: $ 23.68万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9093400
• 关键词: Address; Animals; Apoptosis; Apoptotic; Aspartic Acid; Behavior; Biological Neural Networks; Biosensor; Brain; Caspase; Cell Count; Cell Death; Cell Differentiation process; Cell Proliferation; Cell physiology; Cells; Cellular Stress; Cessation of life; Cleaved cell; Color; Development; Drosophila genus; Equilibrium; Exhibits; Family; Functional disorder; Goals; Injury; Label; Life; Mammals; Mediating; Nerve Degeneration; Neurons; Occupations; Odors; Olfactory Pathways; Pathway interactions; Peptide Hydrolases; Physiological; Presynaptic Terminals; Process; Proteins; Reporting; Role; Stimulus; Synapses; Time; Tissues; behavioral response; cell killing; cell type; experience; fly; in vivo; insight; novel; public health relevance; tool

 DESCRIPTION (provided by applicant): Non-apoptotic caspase activity in neurons Caspases are a family of conserved cysteine proteases that orchestrate apoptotic and pyroptotic cell death. Caspase activity is robustly induced shortly before cell death, and caspase-deficient animals have excess cell numbers. Therefore, activation of caspases is often assumed to represent a commitment point towards cell death. However, mounting evidence indicates that caspases also have non-apoptotic roles in healthy cells and tissues. Mammalian and Drosophila neurons have been reported to use caspases for pruning axonal and dendritic process, which is essential for functional neural networks, potentially by similar mechanisms as apoptosis except spatially restricted. However, fly and mammalian caspases have been implicated in a range of other cellular processes, including cell proliferation and differentiation. Caspase activation has been detected in growing axon terminals, and without evidence of cell death. However, the key unanswered questions remain, including what types of neurons display caspase activity and when. Furthermore, very little is known about the non- apoptotic functions of caspase activity in healthy neurons. A number of different caspase biosensors have been developed to detect caspase activation in neurons and other cell types, however available caspase biosensors are not sufficiently sensitive or sustained to address these questions. Therefore, we developed a new dual color caspase biosensor for Drosophila to detect and study non-apoptotic caspase activity in neurons. We propose to determine which neurons exhibit non-apoptotic caspase, and to establish a role for caspases in normal neuronal function. These studies are needed to gain new insights into the mechanisms that connect the normal versus death functions of caspases, as dysregulation of this balance could contribute importantly to neurodegeneration.

 描述（通过应用证明）：非植物的胱天蛋白酶是半胱氨酸蛋白的家族，thast thast thast thasts thasts thaste thaste thastsent thastsent thastesent thastesent thastement thastesent thastesent thastesent thastesent thastesent thastesent。健康的细胞和树突过程，对于功能性网络至关重要，除了在轴突末端，还可以通过类似的机制与ASPAILY d。剩余的活动，对健康的神经元中的caspase活性的非应用功能很少为了检测和研究神经元中的非凋亡caspase活性。 Ballance Cluckete对神经变性很重要。