Communication between cells is the major business of the nervous system. We are interested in how neuronal communication can be manipulated to treat or prevent neurological and cardiovascular disorders. To achieve this goal we use a combination of molecular, cellular, pharmacological and behavioral approaches, as well as genetically modified mice, to understand how chemical messengers regulate many distinct physiological programs. Of particular interest to us is the role of cholinergic synapses, that release the chemical mediator acetylcholine, in Alzheimer’s disease and in learning and memory. We are also interested in how cholinergic neurotransmission in the peripheral nervous system may be targeted to improve cardiac dysfunction. Finally, we have a strong research program aimed to understand transmissible spongiform encephalopathy, or prion diseases, such as “mad cow disease”. A long-term objective of my research program is to discover ways to manipulate chemical communication to provide novel pharmacological targets to treat these diseases.
• Aline Lara, Denis D. Damasceno, Rita Pires, Robert Gros, Enéas R. Gomes, Mariana Gavioli, Ricardo F. Lima, Diogo Guimarães, Patricia Lima, Carlos Roberto Bueno Jr, Anilton Vasconcelos, Danilo Roman-Campos, Cristiane A.S. Menezes, Raquel A. Sirvente, Vera M. Salemi,Charles Mady, Marc G. Caron, Anderson J. Ferreira, Patricia C. Brum, Rodrigo R. Resende, Jader S. Cruz, Marcus Vinicius Gomez, Vania F. Prado, Alvair P.de Almeida, *Marco A.M. Prado, *Silvia Guatimosim. (2010) Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure. Molecular and Cellular Biology. 30(7):1746-56 *co-senior authors.
• De Castro, B; De Jaeger, X; Martins-Silva, C.; Lima, R.F.; Amaral, E.; Menezes, C.; Lima, P.; Neves, C.M.L; Gould, T.W.; Welch, I; Kushmeric, C.; Guatimosim, C.; Izquierdo,I.; Cammarota, M.; Rylett, R.J.; Gomez, M.V.; Caron, M.G.; Oppenheim, R.W.; Prado, M.A.M*.; Prado, V.F*. (2009) The vesicular acetylcholine transporter is required for neuromuscular development and function. Molecular and Cellular Biology 29: 5238-50. *co-senior authors
• Linden, R., Martins, VR., Prado, M.A.M. (2009) Prion protein UCSD-Nature Molecule Pages doi:10.1038/mp.a003935.01
• Endocytosis of prion protein is required for ERK1/2 signaling induced by stress-inducible protein 1. Caetano FA, Lopes MH, Hajj GN, Machado CF, Pinto Arantes C, Magalhães AC, Vieira Mde P, Américo TA, Massensini AR, Priola SA, Vorberg I, Gomez MV, Linden R, Prado VF, Martins VR, Prado MA. J Neurosci. (2008) 28:6691-702.
• Physiology of the prion protein. Linden R, Martins VR, Prado MA, Cammarota M, Izquierdo I, Brentani RR. Physiol Rev. (2008) 88:673-728.
• Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition. Prado VF, Martins-Silva C, de Castro BM, Lima RF, Barros DM, Amaral E, Ramsey AJ, Sotnikova TD, Ramirez MR, Kim HG, Rossato JI, Koenen J, Quan H, Cota VR, Moraes MF, Gomez MV, Guatimosim C, Wetsel WC, Kushmerick C, Pereira GS, Gainetdinov RR, Izquierdo I, Caron MG, Prado MA. Neuron. (2006) 51:601-12.
• Magalhães AC, Baron GS, Lee KS, Steele-Mortinmer O, Dorward D, Prado MAM*, CAUGHEY B* (2005) Uptake and neuritic transport of scrapie prion protein coincident with infection of neuronal cells. Journal of Neuroscience 25: 5207-5216. (* co-senior authors)
• Magalhães AC, Silva JA, Lee KS, Martins VR, Prado VF, Ferguson SSG, Gomez MV, Brentani RR, Prado MAM (2002) Endocytic intermediates involved with the intracellular trafficking of a fluorescent cellular prion protein. Journal of Biological Chemistry 277: 33311-33318.