Abstract
M1 muscarinic receptors (M 1 mAChR) have an important role in cognitive processing relevant to Alzheimer’s disease brains (AD)1–5. M1 mAChR are relatively unchanged in AD1–5 and therefore may serve as a target for an anti-dementia drug treatment. However, some of the tested muscarinic agonists were not highly M1 selective, had major clinical limitations and showed disappointing clinical results in AD 4,6,7. Thus the proof of clinical concept could not be shown.
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References
J.A. Court JA and E.K. Perry, Dementia: the neurochemical basis of putative transmitter orientated therapy, Pharmac. Ther. 52, 423–443 (1991).
C.J. Ladner and J.M Lee, Pharmacological drug treatment of Alzheimer disease: the cholinergic system revisited, J. Neuropathol. Exptl. Neurol. 57, 719–731 (1998).
E. Perry, J. Court, R. Goodchild, M. Griffiths, E. Jaros, M. Johnson, S. Lloyd, M. Piggott, D. Spurden, C. Ballard, I. McKeith and R. Perry, Clinical neurochemistry: developments in dementia research based on brain bank material, J Neural Transm 105, 915–933 (1998).
A. Fisher, Muscarinic receptor agonists in Alzheimer’s disease: More than just symptomatic treatment. CNS Drugs 12, 197–214 (1999).
A. L. Svensson, I. Alafuzoff and A. Nordberg, Characterization of muscarinic receptor subtypes in Alzheimer and control brain cortices by selective muscarinic antagonists. Brain Res. 596, 142–148 (1992)
A. Fisher, Therapeutic strategies in Alzheimer’s disease: Ml muscarinic agonists, Jap. J. Pharmacol. 84, 101–112 (2000).
J. Pavia, M. de Ceballos, and F.S. de la Cuesta, Alzheimer’s disease: relationship between muscarinic cholinergic receptors, ß-amyloid and t proteins. Fundam. Clin. Pharmacol. 12, 473–481 (1998).
R.M. Nitsch, B.E. Slack, R.J. Wurtman, and J.H. Growdon, Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors, Science 58, 304–307 (1992).
Z. Pittel, E. Heldman, J. Barg, R. Haring, and A. Fisher, Muscarinic control of amyloid precursor protein secretion in rat cerebral cortex and cerebellum. Brain Res. 742, 299–304 (1996).
A.Y. Hung, C. Haass, R.N. Nitsch, W.Q. Qiu, M. Citron, R.J. Wurtman, J.H. Growdon, and D.J. Selkoe, Activation of protein kinase C inhibits cellular production of the amyloid ß-protein. J Biol. Chem. 268, 22959–22962 (1993).
B.A. Wolf, A.M. Wertkin, Y.C. Jolly, R.O. Yasuda, B.B. Wolfe, R.J. Konrad, D. Manning, S. Ravi, J.R. Williamson, and V. M-Y Lee, Muscarinic regulation of Alzheimer’s disease amyloid precursor protein secretion and amyloid ß-protein production in human neuronal NT2N cells. J. Biol. Chem. 270, 4916–4922 (1995).
L. Lin, B. Georgievska, A. Mattsson, and Isacson, O. Cognitive changes and modified processing of amyloid precursor protein in the cortical and hippocampal system after cholinergic synapse loss and muscarinic receptor activation. Proc Natl Acad Sci USA 96, 12108–12113 (1999).
T.G. Beach, P.E. Potter, Y. Kuo, M.R. Emmerling, R.A. Durham, S.D. Webster, D.G. Walker, L.I. Sue, S. Scott, K.J. Layne, and Roher, A.E. Cholinergic deafferentation of the rabbit cortex: a new animal model of Aß deposition, Neurosci. Lett. 31, 9–12 (2000).
T.G. Beach, D.G. Walker, P.E. Potter, and A. Fisher, Reduction of cerebrospinal fluid amyloid beta after systemic administration of Ml muscarinic agonists, Brain Res. 905, 220–223 (2001).
R.M. Nitsch, M. Deng. M. Tennis, D. Schoenfield, and J.H. Growdon, The selective muscarinic Ml agonist AF 102B decreases level of total Aß in CSF of patients with Alzheimer’s diseasc Arch. Neurol. 48, 913–918 (2000).
C. Hock, A. Maddalena, M. Deng, J.M. Growdon, and R.M. Nitsch, Treatment with talsaclidine decreases cerebrospinal fluid levels of total amyloid ß-peptide in patients with Alzheimer’s disease. In: 9 th eeting of the Internat. Stud Group on the Pharmacol of Memory Disorders Associated with .4ging. Zurich, Switzerland. Feb 18–20 (2000).
P.E. Potter, C. Gaughan, and Y. Assouline, Lesion of septal-hippocampal neurons with 1921gG-saporin alters function of Ml muscarinic receptors, Neuropharmacol. 38, 579–586 (1999).
J.F. Kelly, K. Furukawa, S.W. Barger, M.R. Rengen, R.J. Mark, E.M. Blanc, G.S. Roth and M.P. Matson, Amyloid ß-peptide disrupts carbachol-induced muscarinic cholinergic signal transduction in cortical neurons, Proc. Natl. Acad. Sci. 96, 6753–6758 (1996).
E. Sadot, D. Gurwitz, J. Barg, L. Behar, I. Ginzburg, and A. Fisher, Activation of m l -muscarinic acetylcholine receptor regulates — tau phosphorylation in transfected PC12 cells, J. Neurochem. 66, 877–880 (1996).
O.V. Forlenza, J.M. Spink, R. Dayanandan, B.H. Anderton, O.F. Olensen, and S. Lovestone, Muscarinic agonists reduce ι phosphorylation in non-neuronal cells via GSK-3ß inhibition and in neurons, J. Neural. Transm. 107, 1201–1212 (2000).
I. Genis, A. Fisher, and D.M. Michaelson, Site-specific dephosphorylation of ι in apolipoprotein Edeficient and control mice by Ml muscarinic agonist treatment, J. Neurochem. 12, 206–213 (1999).
J. Lucas, F. Hernandez, P. Gomez-Ramos, M.A. Moran, R. Hen, and J. Avila, Decreased nuclear ß—catenin, ι hyperphosphorylation and neurodegeneration in GSK-3ß conditional transgenic mice, EvMBO J. 20, 2739 (2001).
E. Hellstrom-Lindahl, H. Moore H, and A. Nordberg, Increased levels ofι protein in SH-SY5Y cells after treatment with cholinesterase inhibitors and nicotinic agonists ,J Neurochem. 74, 777–784 (2000).
N. Bons, N V. Jallageas, N. Maestre-Frances, S. Silhol, A. Petter, and A. Delacourte, Mcrocebus murinus, a convenient laboratory animal for the study of Alzheimer’s disease, AL-heimer’s Res. 1, 83–87 (1995).
S. Silhol, A. Calenda, V. Jallageas, N. Mestre-Frances, M. Bellis, and N. Bons, Beta-amyloid protein precursor in — icrocebus murinus: genotyping and brain localization, Neurobiol. Dis. 3, 169–182 (1996).
P. Giannakopoulos, S. Silhol, V. Jallageas, J. Mallet, N. Bons, C. Bouras, and P. Delaere, Quantitative analysis of tau protein-immunoreactive accumulations and beta-amyloid protein deposits in the cerebral cortex of the mouse lemur, Microcebus murinus, Acta Neuropathol. 94, 131–139 (1997).
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© 2002 Kluwer Academic / Plenum Publishers, New York
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Fisher, A. et al. (2002). M1 Muscarinic Agonists as a Therapeutic Strategy in Alzheimer’s Disease. In: Mizuno, Y., Fisher, A., Hanin, I. (eds) Mapping the Progress of Alzheimer’s and Parkinson’s Disease. Advances in Behavioral Biology, vol 51. Springer, Boston, MA. https://doi.org/10.1007/978-0-306-47593-1_34
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DOI: https://doi.org/10.1007/978-0-306-47593-1_34
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