Role of A β and the α 7 nicotinic acetylcholine receptor in regulating synaptic plasticity in Alzheimer's disease

Letters in Peptide Science - Tập 10 - Trang 401-404 - 2003
David H. Small1, Lisa R. Fodero2, Dusan Losic3, Cindy Chu4, Marie-Isabel Aguilar1, Lisandra L. Martin5, Mary Chebib6
1Department of Biochemistry and Molecular Biology, Monash University, Australia
2Department of Pathology, University of Melbourne, Australia
3School of Chemistry Physics & Earth Sciences, Flinders University of South Australia, Australia
4Faculty of Pharmacy, University of Sydney, Australia
5School of Chemistry, Monash University, Victoria, Australia
6Faculty of Pharmacy, University of Sydney, NSW, Australia

Tóm tắt

Alzheimer's disease (AD) is caused by the accumulation of β-amyloid protein (Aβ) in the brain. The aggregation of β-amyloid protein to higher molecular weight fibrillar forms is also considered to be an important step in the pathogenesis of the disease. The memory problems associated with AD are likely to be caused by changes in synaptic plasticity. Recent studies suggest that Aβ binds to the α 7 nicotinic acetylcholine receptor (α 7 nAChR), which plays an important role in synaptic plasticity and memory. A loop domain localized towards the C-terminus of the extracellular region of the receptor has been identified as forming part of a putative Aβ-binding site. In cell culture experiments, the binding of Aβ to the α 7 nAChR has been found to cause an increase in the level of acetylcholinesterase, which is also increased around amyloid plaques in the AD brain. These studies indicate that the Aβ-binding site on the α 7 nAChR receptor is an important new target for therapeutic development in AD.

Tài liệu tham khảo

Butters, N., Delis, D.C. and Lucas, J.A., Annu. Rev. Psychol., 46 (1995) 493. Probst, A., Langui, D. and Ulrich, J., Brain Pathol., 1 (1991) 229. Small, D.H. and McLean, C.A., J. Neurochem., 73 (1999) 443. Aguzzi, A. and Haass, C., Science, 302 (2003) 814. Jarrett, J.T. and Lansbury, P.T. Jr., Cell, 73 (1993) 1055. Yankner, B.A., Dawes, L.R., Fisher, S., Villa-Komaroff, L., Oster-Granite, M.L. and Neve, R.L., Science, 245 (1989) 417. Forloni, G., Chiesa, R., Smiroldo, S., Verga, L., Salmona, M., Tagliavini, F. and Angeretti, N., Neuroreport, 4 (1993) 523. Terry, R.D., J. Neuropathol. Exp. Neurol., 59 (2000) 1118. Small, D.H., Mok, S.S. and Bornstein, J.C., Nat. Rev. Neurosci., 2 (2001) 595. Broide, R.S. and Leslie, F.M., Mol. Neurobiol., 20 (1999) 1. Sargent, P.B., Annu. Rev. Neurosci., 16 (1993) 403. Broide, R.S., Robertson, R.T. and Leslie, F.M., J. Neurosci., 16 (1996) 2956. Cheung, N.S., Small, D.H. and Livett, B.G., J. Neurochem., 60 (1993) 1163. Wang, H.Y., Lee, D.H., D'Andrea, M.R., Peterson, P.A., Shank, R.P. and Reitz, A.B., J. Biol. Chem., 275 (2000) 5626. Pettit, D.L., Shao, Z. and Yakel, J.L., J. Neurosci., 21 (2001) RC120. Tozaki, H., Matsumoto, A., Kanno, T., Nagai, K., Nagata, T., Yamamoto, S. and Nishizaki, T., Biochem. Biophys. Res. Commun., 294 (2002) 42. Liu, Q., Kawai, H. and Berg, D.K., Proc. Natl. Acad. Sci. USA, 98 (2001) 4734. Dineley, K.T., Westerman, M., Bui, D., Bell, K., Ashe, K.H. and Sweatt, J.D., J. Neurosci., 21 (2001) 4125. Dineley, K.T., Bell, K.A., Bui, D. and Sweatt, J.D., J. Biol. Chem., 277 (2002) 25056. Wang, H.Y., Li, W., Benedetti, N.J. and Lee, D.H., J. Biol. Chem., 278 (2003) 31547. Sberna, G., Saez-Valero, J., Beyreuther, K., Masters, C.L. and Small, D.H., J. Neurochem., 69 (1997) 1177. Fodero, L.R., Mok, S.S., Losic, D., Martin, L.L., Aguilar, M.I., Barrow, C.J., Livett, B.G. and Small, D.H., J. Neurochem., 88 (2004) 1186. Saez-Valero, J., Sberna, G., McLean, C.A. and Small, D.H., J. Neurochem., 72 (1999) 1600. Small, D.H., Fodero, L.R. and Saez-Valero, J., In Inestrosa, N.C.(Ed.), VIIth International Conference on Cholinesterases, Pucon, Chile, November, 2003. Small, D.H., Curr. Alz. Res., 1 (2004) 27. Vien, J., Duke, R.K., Mewett, K.N., Johnston, G.A.R., Shingai, R. and Chebib, M., Br. J. Pharmacol., 135 (2002) 883.