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We tested whether this pathway is involved in axonal degeneration caused by withdrawal of other trophic support, axotomy or vincristine exposure. Neurturin deprivation, like NGF withdrawal activated this APP\/DR6\/caspase 6 pathway and resulted in axonal degeneration, however, APP cleavage and caspase 6 activation were not involved in axonal degeneration induced by mechanical or toxic insults. However, loss of surface APP (sAPP) and caspase 6 activation were observed during axonal degeneration induced by dynactin 1(Dctn1) dysfunction, which disrupts axonal transport. Mutations in Dctn1 are associated with motor neuron disease and frontal temporal dementia, thus suggesting that the APP\/caspase 6 pathway could be important in specific types of disease-associated axonal degeneration. The NGF deprivation paradigm, with its defined molecular pathway, was used to examine the context of Nmnat-mediated axonal protection. We found that although Nmnat blocks axonal degeneration after trophic factor withdrawal, it did not prevent loss of axon sAPP or caspase 6 activation within the axon, suggesting it acts downstream of caspase 6. These results indicate that diverse insults induce axonal degeneration via multiple pathways and that these degeneration signals converge on a common, Nmnat-sensitive program that is uniquely involved in axonal, but not cell body, degeneration.<\/jats:p>","DOI":"10.1523\/jneurosci.2939-10.2010","type":"journal-article","created":{"date-parts":[[2010,10,13]],"date-time":"2010-10-13T17:09:19Z","timestamp":1286989759000},"page":"13729-13738","source":"Crossref","is-referenced-by-count":97,"title":["Amyloid Precursor Protein Cleavage-Dependent and -Independent Axonal Degeneration Programs Share a Common Nicotinamide Mononucleotide Adenylyltransferase 1-Sensitive Pathway"],"prefix":"10.1523","volume":"30","author":[{"given":"Bhupinder P. 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