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Caspases in p75-mediated Neuronal Death Pathway. Cell Death Necrosis –Response to disease –Inflammatory Response Apoptosis –Present in Developing Tissue.

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Presentation on theme: "Caspases in p75-mediated Neuronal Death Pathway. Cell Death Necrosis –Response to disease –Inflammatory Response Apoptosis –Present in Developing Tissue."— Presentation transcript:

1 Caspases in p75-mediated Neuronal Death Pathway

2 Cell Death Necrosis –Response to disease –Inflammatory Response Apoptosis –Present in Developing Tissue –Absence of Inflammatory Response –Mediated by certain pathways

3 Details of the p75-mediated Cell Death Pathway NGF p75 Receptor Mitochondria (Cytochrome C, Adaptor Protein-Apaf1, & Smac/Diablo) MIAP3 Caspase 9 Caspase 6 Caspase 3

4 p75-Mediated Pathway

5 NGFNGF Neuronal Death NGF binds to the p75 receptor. This death receptor initiates the mitochondrial pathway for cell death.Membrane p75

6 NGFNGF Neuronal Death The binding then causes the blocking of certain mitochondrial molecules such as BCL-2. This then allows cytochrome C to leave the mitochondrion. Cyt C

7 N G F Neuronal Death Cytochrome C and apaf1, an adaptor protein, bind and activate caspase 9. Cyt C Apaf 1 C9

8 N G F Neuronal Death At the same time that Cytochrome C is being released, the mitochondrion also releases Smac/Diablo. S/D blocks MIAP. C9 Cyt C Apaf 1 Smac/ Diablo MIAP

9 N G F Neuronal Death Caspase 9 activation leads to the activation of caspase 6 and 3. C9 Cyt C Apaf 1 Smac/ Diablo MIAP C6C3

10 N G F Neuronal Death Activation of Caspase 3 and Caspase 6 leads to neuronal death. C9 Cyt C Apaf 1 Smac/ Diablo MIAP C6C3

11 How did we simplify the pathway for a math model? Group cellular events together –Caspases 9 and 6 Eliminate upstream regulatory proteins –Cyt C, Apaf 1, Smac/Diablo

12 N G F Neuronal Death MIAP C6C3 1.p75 bound and there is no excitation between C3 and C6. What are the conditions for the cell to live? 2.p75 bound and there is excitation between C3 and C6. What are the conditions for the cell to die? First Model: Vary Connection Between C6 and C3

13 N G F Neuronal Death MIAP C6C p75 bound the connection between p75 and C6 is absent. What are the conditions for the cell to live? 2. 2.p75 bound the connection between p75 and C6 is present. What are the conditions for the cell to die? Second Model: No Excitation Present Between C6 and C3 – Vary connection between p75 and C6

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