Affiliations: [a] Departamento de Bioquímica y Biología molecular IV, Facultad de Óptica, Universidad Complutense de Madrid, Madrid, Spain | [b] Centro de Biología Molecular “Severo Ochoa”, CSIC- Universidad Autónoma de Madrid, CIBERNET, Madrid, Spain | [c] Departamento de Bioquímica y Biología Molecular IV, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain | [d] Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain
Correspondence:
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Correspondence to: Miguel Díaz-Hernandez, Departamento de Bioquimica y Biología Molecular IV, Facultad Veterinaria, Universidad Complutense de Madrid, Av. Puerta de Hierro s/n, 28040 Madrid, Spain. Tel.: +34 91 3944068; Fax: +34 91 3943909; E-mail: migueldiaz@vet.ucm.es; Jesus Pintor, Departamento de Bioquimica y Biología Molecular IV, Facultad Optica y Optometría, Universidad Complutense de Madrid, C/Arcos de Jalon 118, 28037 Madrid, Spain. Tel.: +34 91 3946859; Fax: +34 91 3946885; E-mail: jpintor@vet.ucm.es.
Abstract: In recent years, in vitro experiments have shown that the spread of Alzheimer's disease is caused by a non-conventional activation of muscarinic receptors by dephosphorylated extracellular tau protein. However, so far, in vivo data to support this hypothesis has not been obtained. The eye provides a good model where cholinergic (muscarinic) transmission can be analyzed. The role of muscarinic receptors in the stimulation of lacrimal gland secretion has already been described, and it has been suggested that acetylcholine is the main transmitter controlling tear secretion. In this project, we have studied the interaction between tau and muscarinic receptors by analyzing tear secretion in the eyes of white rabbits. Our results show that tau protein increases tear secretion by 47.2% in a similar way to a muscarinic receptor agonist carbachol (84.3%). The use of muscarinic antagonists indicated that tau interacts with M1 and mainly M3 muscarinic receptors. In summary, tau can bind muscarinic receptors in vivo and this may explain the spread of the pathology.
