Journal
EUROPEAN NEUROPSYCHOPHARMACOLOGY
Volume 19, Issue 10, Pages 708-717Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.euroneuro.2009.04.006
Keywords
Tau protein; Alzheimer; Muscarinic receptors
Funding
- Spanish Ministry of Health [SAF 2006-02424]
- Ciberned [CB06/05/0035]
- Noscira [2008/285]
- Comunidad de Madrid [SAL/0202/2006]
- Fundacion M. Botin and Fundacion R. Areces
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It was recently suggested that tau protein released as a result of neuronal death is toxic to neighbouring cells, an effect that is mediated through the activation of muscarinic M1 and/or M3 receptors. Nevertheless, why tau protein and not other native muscarinic agonists, like ACh, can induce this neurotoxicity remains unknown. To clarify this issue, we analysed the different responses and properties of muscarinic receptors in response to stimulation by tau or ACh. The results revealed that the tau protein has an affinity for muscarinic receptors of around one order of magnitude higher than that of ACh. Furthermore, white the repeated stimulation with ACh induces desensitization of the muscarinic receptors, reiterate stimulation with tau failed to produce this phenomenon. Finally, we found the tau protein to be very stable in the extracellutar milieu. These studies provide valuable information to help understand tau toxicity on neural cells bearing M1 or M3 muscarinic receptors and its contribution to neurodegenerative progression in tauopathies. (C) 2009 Elsevier B.V. and ECNP. All rights reserved.
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