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1、Aberrant Neuregulin 1 Signaling in Amyotrophic Lateral Sclerosis Lu Ke Class c4 178112177OUTLINE Introduction Materials and Methods Results DiscussionIntroduction Amyotrophic lateral sclerosis(ALS 肌萎缩性脊髓侧索硬化症) is a progressive neurodegenerative disease that affects nerve cells in the brain and the s

2、pinal cord. The pathogenesis of ALS is poorly understood, and there are presently no effective therapies to stop its insidious progression. Introduction Neuregulin 1 (NRG1) is a neuron-derived trophic molecule that supports axoglial and neuromuscular development through several alternatively spliced

3、 isoforms Its possible role in the pathogenesis and progression of amyotrophic lateral sclerosis (ALS) is not known. Can NRG1 be a novel therapeutic target against disease progression in ALS ?MATERIALS AND METHODS Human Tissue Fresh-frozen thoracic and lumbar spinal cords from 6 sporadic and 2 famil

4、ial ALS subjects and 6 control patients. SOD1 Mouse Tissue（过氧化物歧化酶1转基因小鼠） Thoracic and lumbar spinal cord regions were collected from each mouse at different stages (preclinical / disease onset / end-stage disease). 4 to 8 mice were used per group at each time point (4 time points, 32 mice in total)

5、.MATERIALS AND METHODS Histopathology Immunohistochemistry Immunoblotting Quantitative Image Analysis Isolation and Real-time Quantitative Reverse Transcription-Polymerase Chain Reaction Statistical AnalysisRESULTSRESULTS NRG1 Receptor Activation on Microglia NRG1 Receptor Activation on Microglia During SOD1 Disease Progression and in During SOD1 Disease Progression and in ALSALSDISCUSSION NRG1-Induced Microglial Activation as a Possible Therapeutic Target for ALS Different Roles for Alternatively Spliced Iso