App neural function


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App neural function

  1. 1. Amyloid Precursor Protein (APP) The effects of overproduction in Alzheimer’s and Downs Syndrome Taylor Griffith, Rachel Christman, Shanley Besett, Christa Franz
  2. 2. Down’s Syndrome <ul><li>trisomy 21 </li></ul><ul><li>poor neuron growth </li></ul><ul><li>early neuron death </li></ul><ul><li>an inability to produce new synapses (an important component of learning) </li></ul>
  3. 3. APP: Lecture Connection <ul><li>• APP is an integral transmembrane protein coded for on chromosome 21 </li></ul><ul><li>Other genes code for proteases that normally cleave this protein into smaller peptides used for cell signaling </li></ul><ul><ul><li>• cell movement in embryonic development, synapse formation & neural plasticity </li></ul></ul><ul><ul><li>normal apoptosis (programmed cell death) </li></ul></ul><ul><ul><li>repair following neural injury </li></ul></ul><ul><li>However, elevated levels of APP (and therefore the products of cleavage) can lead to disease </li></ul>p. 283
  4. 4. Over Expression of APP <ul><li>• With abnormal levels of APP, as seen in Downs Syndrome (trisomy 21) and Alzheimers, these cleaved peptides accumulate in the ECF and can impede normal neural growth, repair, cell signaling, and differentiation </li></ul><ul><li>• These deposits of peptides are called amyloid plaques (shown below) </li></ul><ul><li>• These plaques lead to the death of neurons especially in the hippocampus which is the major center for learning and memory </li></ul>
  5. 5. Membrane Protein  Plaque Cut pieces of APP aggregate in ECF as amyloid plaque and can signal cell death Integral transmembrane protein Proteases lyse APP into components that enter either the ICF or ECF Figures retrieved 4/16/08:
  6. 7. Analogy…The Deadliest Catch <ul><li>APP are like boats in the ocean </li></ul><ul><li>Some boats are good to control crab population but if there are too many, too many crabs die and pollution accumulates </li></ul><ul><li>Pollution=plaques </li></ul><ul><li>Crabs= Neurons </li></ul><ul><li>Boats=APP </li></ul>
  7. 8. References <ul><li>Isacson, O., Seo, H., Lin, L., Albeck D., & Granholm A. (2002). Alzheimer’s disease and Down’s syndrome: roles of APP, trophic factors and ACh. Trends in Neurosciences , 25 , 79-82. </li></ul><ul><li>Priller, C., Bauer T., Mitteregger G., Krebs, B., Kretzschmar, H. A., & Herms, J. (2006). Synapse formation and function is modulated by the amyloid precursor protein. Journal of Neuroscience , 26 , 7212-7221. </li></ul><ul><li>Salehi, A. (2006). Down Syndrome; Cause of neuronal death in down syndrome, Alzheimer’s disease could be surprisingly simple. Biotech Week, p. 494. </li></ul><ul><li>Turner, P.R., O’Connor, K., Tate, W. P., Abraham, W.C. (2003) Roles of amyloid precursor protein and its fragments in regulation neural activity, plasticity, and memory. Programming Neurobiology , 70, 1-32. </li></ul><ul><li>Busciglio, J., Pelsman, A., Wong, C., Pigino, G., Yuan, M., & Mori, H . (2002). Altered metabolism of the amyloid ß precursor protein is associated with mitochondrial dysfunction in Down’s syndrome. Neuron, 33, 677-688. </li></ul><ul><li>Selkoe, D. J. (1998). The cell biology of ß-amyloid precursor protein and presenilin in Alzheimer’s disease. Cell Biology , 8 , 447-453. </li></ul><ul><li>Strooper, B. D. & Annaert, W. (2000). Proteolytic processing and cell biological functions of the amyloid precursor protein. Journal of Cell Science , 113 , 1857-1870. </li></ul><ul><li>Ober, W. C., Garrison, C. W., Silverthorn A. C., & Johnson, B.R. (2007). Human Physiology: An Integrated Approach, Fourth Edition. San Francisco: Pearson . </li></ul><ul><li>Lodish, H., Berk, A., Kaiser, C. A., Krieger, M., Scott, M. P., Bretscher, A., et. al. (2008). Molecular Cell Biology: Sixth Edition . New York: W.H. Freeman and Company </li></ul>