Marco Antonio Maximo Prado, Scientist
Why I Became a Scientist
I was fascinated with chemical kits as a child; then when I attended Pharmacy school I became intrigued by how neurons communicate with each other and with target organs. The possibility to answer fundamental questions on neuronal communication that can provide novel treatments for diseases has driven my interests in research since then.
Research Summary
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.
Research Questions and Disease Implications
The prion protein has emerged as a major player to organize communication in the brain. The protein can change shape and this causes disease. Recent work has provided novel evidence for a role of prion protein in Alzheimer’s disease. However, how signalling by the prion protein influences neurological disorders is unknown.
Our research will uncover fundamental mechanisms by which neurons use the prion protein to communicate and may provide novel ways to treat Alzheimer’s and prion diseases.
In Alzheimer’s disease the chemical messenger acetylcholine is decreased and neurons are unable to maintain normal levels of acetylcholine secretion. How this affects cognitive processing in Alzheimer’s disease? How acetylcholine regulates hippocampal function?
This work will provide novel information on how acetylcholine regulates brain functions. We will also learn if it is possible to manipulate the machinery used to secrete acetylcholine to increase its activity in the brain.
Acetylcholine is the major chemical messenger regulating autonomic functions. Cholinergic neurons regulate most of our bodily functions, but in certain diseases such as diabetes and dysautonomy these neurons cannot function well. What happens when neurons that control the heart go awry? How the autonomic system shapes heart function in the long-term?
This research has started to uncover novel mechanisms that regulate long-term activity of the heart and has implications to develop novel treatments for heart failure.
Education
• Pharmacy; MSc Biochemistry; PhD Biochemistry; Diploma Cell Biology
Training
• UFMG; McGill University; Duke University
Awards
• Senior Research Fellow National Research Council (Brazil, 1995-2008)
• IBRO fellow (2003)
• John Simon Guggenheim Fellow (2005)
Publications
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.
The "ins" and "outs" of the high-affinity choline transporter CHT1. Ribeiro FM, Black SA, Prado VF, Rylett RJ, Ferguson SS, Prado MA. J Neurochem. (2006) 97:1-12
Structural requirements for steady-state localization of the vesicular acetylcholine transporter. Ferreira LT, Santos MS, Kolmakova NG, Koenen J, Barbosa J Jr, Gomez MV, Guatimosim C, Zhang X, Parsons SM, Prado VF, Prado MA. J Neurochem. (2005) 94:957-69.
Contact Information
Robarts Research Institute
The University of Western Ontario
P.O. Box 5015, 100 Perth Drive
London, ON N6A 5K8
Tel: 519-663-5777 Ext. 24888
Fax: 519-663-3789
mprado@robarts.ca