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| First Name: | Rafael | | Last Name: | Rodríguez Puertas | | Title: | Dr. | | Advanced Degrees: | BS, PhD | | Affiliation: | Research Scientist | | Department: | Pharmacology | | Street Address 1: | Fac. Medicine. Univ. of the Basque Country (UPV-EHU) | | Street Address 2: | Campus de Leioa. Barrio Sarriena | | City: | Leioa | | State/Province: | Vizcaya | | Zip/Postal Code: | 48940 | Country/Territory: | Spain | | Phone: | 34 94 6012739 | | Fax: | 34 94 6013220 | | Email Address: |  |
Disclosure:
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View all comments by Rafael Rodríguez Puertas
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Molecular and Cell biology, Chemistry/Pharmacology, Neurotransmission, Protein structure/chemistry, Proteomics, Drug screening, Signal transduction, Microscopy, Animal Models
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-Bachelor in Biochemistry, Univ. of the Basque Country, Spain. 1990.
-PhD in Pharmacology, Univ. of Cantabria Santander, Spain. "chollinergic system in Alzheimer disease and Parkinson disease" .1995. Director: Prof. Angel Pazos
- Postdoctoral research at the Dept. of Neuroscience. Karolisnka Institute. Stockholm, Sweden. 1995-1998. Prof. Tomas Hökfelt' s group.
-Senior Scientist. Dept. Pharmacology, Univ. of the Basque Country, Spain. From 1998. |
Rodríguez-Puertas, R., Pazos, A., Zarranz, J.J., Pascual, J. Selective cortical decrease of high-affinity choline uptake carrier in Alzheimer disease: an autoradiographic study using 3H-hemicholinium-3. Journal of Neural Transmission (Parkinson-Dementia Section) 8: 161-169, 1994.
Rodríguez-Puertas, R., Pazos, A., Pascual, J. Effects of freezing storage time on the density of muscarinic receptors in the human postmortem brain: an autoradiographic study in control and Alzheimer’s disease brain tissues. Brain Research, 728: 65- 71, 1996.
Rodríguez-Puertas, R., Nilsson S., Pascual, J., Pazos, A., Hökfelt, T. 125I-galanin binding sites in Alzheimer’s disease: increases in hippocampal subfields and a decrease in the caudate nucleus. Journal of Neurochemistry, 68: 1106-1113. 1997.
Rodríguez-Puertas, R., Pascual, J., Vilaró, T., Pazos, A. Autoradiographic distribution of M1, M2, M3 and M4 muscarinic receptor subtypes in Alzheimer’s disease. Synapse, 26: 341-350. 1997.
Rodríguez-Puertas, R., Herrera-Marschitz M., Hökfelt T. Dopamine D1 receptor modulation of glutamate receptor messenger RNA levels in the neocortex and neostriatum of unilaterally 6-hydroxidopamine-lesioned rats.Neuroscience, 89(3): 781-797. 1999.
Rodríguez-Puertas, R., González-Maeso J., Meana J.J., and Pazos A. Autoradiography of receptor-activated G-proteins in postmortem human brain. Neuroscience, 96: 169-180. 2000.
J. González-Maeso, R. Rodríguez-Puertas, A.M. Gabilondo, J.J. Meana. Characterization of receptor-mediated [35S]GTPgS binding to cortical membranes from postmortem human brain. European Journal of Pharmacology, 390: 25-36. 2000.
González-Maeso J., Torre I., Rodríguez-Puertas R., García-Sevilla J.A., Gimón J., Meana J.J. Effect of age, postmortem delay and freezing storage time in receptor-mediated activation of G-proteins in postmortem human brain. Neuropsycopharmacology 26(4): 468-478. 2002.
González-Maeso J., Rodríguez-Puertas R., Meana J.J. Quantitative stoichiometry of G-proteins activated by µ-opioid receptors in postmortem human brain European Journal of Pharmacology 452 (1): 31-43. 2002.
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The cause:
-Why some old people develop Alzheimer's
Disease and others doesn't?.
- Why are the cerebral memory related areas primarily and selectively affected?
- Why is the cholinergic neurotransmitter system the main neurotransmision impairment, at least at the initiation of the disease?
- Are the tau hyperphosphorilation and the beta-amiloid deposition a cause or a consequence of the AD? |
Buxhaum J.D., Oishi M., Chen H.I. Cholinergic agonists and interleukin 1 regulate prosessing and secretion of the Alzheimer Beta/A4 amyloid protein precursor. Proc. Natl. Acad. Sci. USA, 1992, 89: 10075-78.
Nitsch R.M., Growdon J.H. Role of neurotransmission in the regulation of amyloid beta-protein precursor processing. Biochem. Pharmacol. 1994, 47: 1275-1284.
Trojanowski J.Q., Schmidt M.L., Shin R.W., Bramblett G.T., Rao D., Lee V.M. Altered tau and neurofilament proteins in neuro-degenerative diseases: diagnostic implications for Alzheimer's disease and Lewy body dementias. Brain Pathol. 1993, 3(1):45-54.
Auld D.S., Satyabrata K., Quirion R. beta-amiloid peptides as direct cholinergic neuromodulators.Trends Neurosci., 1998, 21:43-49.
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1- Elucidate the real influence of the tau hyperphosphorilation and the beta-amiloid deposition in the neurotranmision impairment. Specifically in the cholinergic system. The main goal would be to Know if the histophatological markers of the AD are the cause or a consecuence of the neurotranmision impairment.
Animal models would be used trying to produce similar nerotransmision lesions, to hypothetically induce tau hyperphosphorilation and/or the beta-amiloid deposition.
And the opposite, induce tau hyperphosphorilation and/or the beta-amiloid deposition in animal model (transgenic etc...) and evaluate the different neurotransmitter systems functionality.
In addtion the learning and memory parameters would be studied in these animals.
2-Study the correlation of both, neurotransmitter impairment and histophatological markers of the AD in human brain tissue. Postmortem tissue, PET scaner, biopsies...
In this second study the information about cognitive impairment of the AD patients, and pharmacological treatments should be evaluated and correlated with the neurochemical and histological information.
3- a genetic map of the AD patients, using in a first step microarrays systems, and second the expresion of the proteins that codify for that genes.
4- a very detailed demographic study about every possible characteristic about the life of the AD patients, focusing in the environment , and food. |
Tau hyperphosphorilation and/or the beta-amiloid deposition are not the cause but a consequence of a primary impairment of the right neural transmission. The already reported specific impairment of some neurotransmitter systems as the cholinergic, and the specificity of the brain areas damaged in the AD should be reevaluated. It is clear that not all the neurons are equally affected in the AD. We shoud identify the specific neurochemical characteristics of those areas
and their signaling routes.
On the other hand, the cause of the AD could be some missing factor that ultimately is affecting the neuronal membrane integrity and conectivity. |
-Show clearly that Tau hyperphosphorilation and the beta-amiloid protein deposition can be produced by a cholinergic (or other neurotransmitter system) modulation.
-Find the substances that can induce the neurotransmission impairment, and as a result, an "AD like" learning and memory impairment. |
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