Principal investigator: Prof. Paolo Zatta
|
|
METAL IONS AND THE BRAIN
Principal investigator: Prof. Paolo Zatta
|
|
External collaborations:
Prof. Tamas Kiss, Department of Inorganic Chemistry, JATE University, Szeged,
Hungary;
Prof Thanos Salifoglu, Department of Chemistry, University of Crete,
Greece;
Dr Luigi Messori, Chemistry Department, University of Florence, Italy;
Prof. Emilio Carpene', Department of Veterinary, University of Bologna, Italy;
Dr Mario Suwalsky, Chemistry Department, University of Concepcion, Chile;
Dr Riszard Lobinski, CNRS, Pau, France
Prof. Beka Solomon, Department of Biotechnologies, University of Tel Aviv,
Israel
Prof. Ombretta Mameli, Department of Physiology, University of Sassari, Italy
Dr Guy Berthon, CNRS, University Paul Sabatier, Toulouse, France
Introduction
Metal ions, as well as proteins, lipids, carbohydrates and vitamins, are an essential part in the life processes. In this connection, while the relevant role played in biological systems, by some metal ions has been relatively well established, for other elements the scenario is almost totally obscure. Elements, for instance as Al, Ba, Bi, Ge, Li, Pb, Rb, Ti, and others do not meet the requirement for "essentiality", at least so far. Thus, they are present in living organisms in that they may have been acquired through contact with environment by physical or chemical processes in competition with other essential elements for their binding sites in biological systems. The movement of an ion in a membrane, and particularly, its movement to and from water, will be dependent on the rate at which water leaves and enters the coordination sphere of an ion. The biophysical properties related to the coordination sphere of a metal that justify its biological action represent a field of great interest and importance nowadays called metal speciation.
Neurotoxicological events produced by metal ions as Pb, Hg, Sn, Mn, and few others, have been quite well elucidated. Diversely, several neuropathological, mainly neurodegenerative, events connected with an abnormal homeostasis or with an abnormal accumulation of metal ions in the brain have so far to be clarified. Neuropathologies for instance like Dialysis dementia, Parkinson's disease, Alzheimer's disease, Amyothrophic lateral sclerosis, Wilson's disease and other present a peculiar abnormal accumulation of metal ion/s in specific brain areas characteristic for the metal ion accumulated and for the specific pathology considered. The connection between metal ions dimetabolism and neuropathological events is a very active research area and a matter of an interdisciplinary study carried out in this laboratory since 1985.
Presently, we are dealing with three research lines with the aim to better understand the molecular mechanisms that could elucidate the physiopathological role of some metal ions in connection with some neurological diseases.
1. Aluminum Physiopathology
Al is the most abundant metal ion in the biosphere, but it is considered to have no definite biological role. However, according to R.P.J. Williams, perhaps because the effects of its deficiency has not been sufficiently tested or because the requirement is so low, and present even in carefully purified diet. Anyhow, preliminary experiments carried out in this and other laboratories seem to indicate that aluminum could have some trophic properties at least in some cell cultures. Diversely, from a neurotoxicological point of view, aluminum is an ascertained neurotoxic agent for animals and man and, an established etiological factor in some pathologies related to dialysis treatment of uremic subjects (e.g., dialysis encephalopathy)(DE). In DE, aluminum accumulates in all brain mass: many neurons are shrunken with hyperchromatic nuclei and loss of Nissl substance, especially in the outer granular layer. In addition, an enlargement of microglial and astroglial proliferation has also been noted. Furthermore, a spongiform change proliferation of neuropil together with neurofibrillary degeneration has been described in some patients with DE. Individual suceptibility to aluminum appear to play a relevant role to exacerbate the neuropathological role of aluminum. Vaccines, for instance, containing aluminum as an adjuvant, can produce glanulomas in sensitive subjects. Other pathologies have been related, but so far without clear evidences, to aluminum accumulation as Parkinson's disease, Alzheimer's disease, Amyothrophic lateral sclerosis, and others, in that abnormal accumulation of metal ion has been seen in the features that characterize such pathologies.
Projects underway
A) A novel low molecular weight protein highly expressed in neuroblastoma
cell line after long-term adaptation to subtoxic Al(III) concentration has
been recently identified in our laboratory. In collaboration with Dr R.
Lobinski's laboratory (CNRS, Pau, France), we are trying to isolate and
characterize such a protein.
B) A significant increased frequency of a genetic variant of transferrin (TfC2) in association with Alzheimer's disease has been recently observed by three indipendent laboratories. In collaboration with Dr S. VanRensburg (Stellenbosch, South Africa) who first reported such a variation in a small number of AD subjects, we are trying to reproduce such findings in a larger selected population of AD patients. When the results will be confirmed, the isolation and characterization of TfC2 from AD and uremic patients will be persue to understand if such TfC2 genetic variant presents different properties in binding Al(III) and Fe(III) and thus modify the metals transport in the brain or if it plays any role in b-amyloid deposition.
C) Several biochemical studies are in progress in our laboratory to better understand the role played by Al(III) on the activity of some key enzymes alterated in AD (Acetylcholinesterase, Enzymes of Krebs cycle, Glutamate dehydrogenase, etc.), together with studies on the pro-oxidant role played by Al(III) in the peroxidation of cellular membranes concomitanly with the presence of bA4 amyloid that accumulates in the neurons, plaques and tangles in AD.
2. Titanium
Titanium, is the ninth most abundant element in the litosphere. It occurs widely in the environment; it is present in urban air, rivers, drinking water and in many foods. Approximately 3% of an oral dose of Ti is absorbed, but the majority is excreted in urine (10 µg/L).The body burden of Ti has been estimated in 15 mg. Titanium dioxide, the most widely used compound, is a white pigment used in paints, as a food additive to whiten flour, diary products, and confections, as well as whitener in cosmetic products. Because its resistance to corrosion and inertness it has many metallurgical applications as in surgical implants and protheses. Most of its forms are very insoluble in water. The common oxidation state is Ti4+. In human body Ti concentration is highly variable and in the brain the mean concentration is around 0.2 µg/g fresh tissue (9). Recently, we have observed that Ti(IV), from Ti-citrate preparation, binds to human transferrin and towards this complexation could be transported, in various tissues, even into the brain. Preliminary experiments, carried out in this laboratory in collaboration with other national and international laboratories, have shown that Ti, administered to mice in drinking water as Ti-citrate and Ti-ascorbate, can contribute significatively to the animal growth in a metal speciation dependent manner. Chemical and biophysical characterization (spectroscopic, potentiometric studies, X-ray diffraction etc.) of our Ti compounds as well as the effects produced in experimental animals are in progress. (Coll.: Prof. I. Pais, Dr A. Salifoglou, Dr. L. Messori).
3. Metallothioneins
Metallothioneins (MTs) represent a group of intracellular, low molecular weight, cystein rich and ubiquitous proteins. Human Mts are encoded by a complex multigene family located on chromosome 16, which includes two functional MT-I gene and a functional MT-II gene. The physiological function of Mts are not well understood. In brains, Mts are expressed in three isoforms. MT-I, MT-II and MT-III. MT-I and MT-II are in the pia mater, ependymal cells, astrocytes, glial processes and fibrous astrocytes, in the white matter in the telencephalon. They appear to be totally absent in neurons, oligodendroglia and microglia in all areas of the brain. In cerebellum, Mts were detected in the Bergmann cells, in protoplasmic astrocytes of the granular layer and in the fibrous astrocytes of the white matter. In contrast, MT-III, appears to be expressed exclusively in neurons, especially the zinc-containing neurons of the hippocampus, and appears to be absent from glial cells. There is a general consensus on the role of Mts in copper and zinc homeostasis, as well as a protective role against cytotoxicity of biophysical and chemical origin such as that induced by metal ions, reactive oxygen species, mutagens and radiations. In the neurodegenerative disease as Alzheimer's disease (AD), astrocytes become abundant and activated in the affected areas. They are especially prominent in the II-VI layers of the frontal cortex as well as in the hippocampus and in the outer molecular layer of the dentate gyrus. Recently, we have demonstrated that MT-I-II are highly expressed in the brain of subjects affected by Alzheimer's disease (Zambenedetti et al., (1998) J. Chem. Neuroanat. 15: 21-26). Results showed that expression of these proteins in the cortex, cerebral white matter and cerebellum is a relevant anatomopathological characteristic of AD. MT-I-II in AD are present in astrocytes and microcapillaries, in the granular but not in the molecular layer of the cerebellum. Work is in progress to identify also the expression of MT-III in AD as well as in other neuropathologies characterized by astrocytosis. (Coll.: Prof. J. Hidalgo, Prof. E. Carpene').
PUBLICATIONS (1994-2002)
INTERNATIONAL FULL PAPERS
1. Zambenedetti P., Tisato F., Zatta P. and Corain B. (1994) The reactivity of aluminum(III) with membrane phospholipids. A NMR approach. Biometals 7: 244-252.
2. Favarato M., and Zatta P. (1994) Histofluorimetric aluminum determination in Alzheimer's disease brain. In: Aluminum in Chemistry, Biology and Medicine. vol. 2, Life Chemistry Reports (Special issue) Nicolini M., Zatta P. and Corain B. (eds). Harwood Acad. Publ. GmbH, London, pp. 71-78.
3. Zatta P., Zambenedetti P. and Cervellin D. (1994) Neuroblastoma cells: an aluminum(III) cytotoxicological model. In: Aluminum in Chemistry, Biology and Medicine. vol. 2, Life Chemistry Reports (Special issue) Nicolini M., Zatta P. and Corain B. (eds). Harwood Acad. Publ. GmbH, London, pp. 111-123.
4. Bragadin M., Dell'Antone P. and Zatta P. (1994) Inhibitory effect of aluminum on H+-ATPase in isolated lysosomes. In: Aluminum in Chemistry, Biology and Medicine. vol. 2, Life Chemistry Reports (Special issue) Nicolini M., Zatta P. and Corain B. (eds). Harwood Acad. Publ. GmbH, London, pp. 165-169.
5. Corain B., Sheik-Osman A.K., Bertani R., Tapparo A and Zatta P. (1994) The aqueous solution state of a-hydrocarboxylate complexes of aluminum(III): an IR and NMR approach. In: Aluminum in Chemistry, Biology and Medicine. vol. 2, Life Chemistry Reports (Special issue) Nicolini M., Zatta P. and Corain B. (eds). Harwood Acad. Publ. GmbH, London, pp. 103-109.
6. Zatta P., Zambenedetti P. and Masiero S. (1994) Effects of aluminum lactate on murine neuroblastoma. NeuroToxicology 15: 789-798.
7. Zatta P., Zambenedetti P., Bruna V. and Filippi B. (1994) Activation of acetylcholinesterase by Al(III): relevance of the metal speciation. Neuro Report 5: 1777-1780.
8. Zatta P., Cervellin D., Favarato M., Gerotto M. and Mattiello G. (1994) Microelemental concentration in the ontogenesis of rat brain. Trace Elem. Med. 11: 143-147.
9. Zatta P. (1995) Aluminum binds to hyperphosphorylated Tau in Alzheimer's disease. A hypothesis. Medical Hypothesis 44: 169-172.
10. Dell'Antone P., Bragadin M. and Zatta P. (1995) The accumulation of tacrine in the acidic compartments of the cell. Biochim. Biophys. Acta. 1279: 137-141.
11. Tapparo A., Solda' L., Bombi G.G., Zambenedetti P., Zatta P., Bertani R. and Corain B. (1995) Analytical validation of a general protocol for the preparation of dose-controlled solutions in aluminum toxicology. Analyst 120: 2425-2429.
12. Zatta P., Zambenedetti P., Pizziuti A. and Perazzolo M. (1995) Different effects of aluminum(III) upon carbonic anhydrase and Na+/K+-ATPase. Neurosc. Lett. 197: 1-4.
13. Zatta P., Zambenedetti P., martuyrano B., Palumbo M. and Nicolini M. (1995) Effects of tacrine upon murine neuroblastoma cells. J. Neuron. Transm. 102: 113-123.
14. Zatta P. (1996) A new bioluminescent assay for studies of protein G and protein A binding to IgG and IgM. J. Biochem. Biophys. Meth. 32: 7-13.
15. Zatta P., Zambenedetti P. and dell'Antone P. (1996) Differential uptake of tacrine and physostigmine by murine neuroblastoma cells. Med. Sci. Res. 24: 363-365.
16. Zatta P. and Zambenedetti P. (1996) Aluminum speciation and morphological differentiation in murine neurobalstoma cells. Biol. Trace Elem. Res. 51: 77-85.
17. Zambenedetti P., Giordano R. and Zatta P. (1996) Identification of lectins' receptors in rat brain. Glycoconjugate J. 13: 341-346.
18. Zatta P. and Zambenedetti P. (1996) Effects of aluminum on neuroblastoma cells culture: Relevance of the metal speciation. Proc. Intern. Symp. on: New Perspectives in the Research of Hardly Known Trace Elements and Their Role in Life Processes. (I. Pais, ed). Budapest, pp. 179-186.
19. Zatta P., Zambenedetti P., Toffoletti A., Corvaja C. and Corain B. (1997) Aluminum(III) induces alterations on the physical state of the erythrocytic membrane. An ESR evaluation. J. Inorg. Biochem. 65: 109-114.
20. Zatta P., Zambenedetti P., Giordano R. and Favarato M. (1997) Rabbit spinal cord infactuated upon Al(III) liposomes intravenous treatment. J. Trace Elem. Med. Biol. 11: 170-172.
21. Zatta P. (1997) Biological models for the study of aluminum neurotoxicity. Acta Medica Romana 35: 592-600.
22. Zatta P., Nicosia V. and Zambenedetti P. (1998) Evaluation of MAO activities on murine neuroblastoma cell upon acute or chronic treatment with aluminum(III) or tacrine. Neurochem. Intern. 32: 273-279.
23. Zatta P., Cervellin D. and Zambenedetti P. (1998) Effects of aluminum speciation on the morphjology of rabbit erythrocytes: a toxicological model. Toxicol. in vitro. 12: 287-293.
24. Zambenedetti P., Giordano R. and Zatta P. (1998) Metallothioneins are highly expressed in astrocytes and microcapillaries inAlzheimer's disease brain. J. Chem. Neuroanat. 15: 21-26.
25. Zatta P., Zambenedetti P. and Milacic R. (1998) Aluminum toxicity: the relevant role of the metal speciation. Analusis. 26: M54-M58.
26. Zatta P. (1998) Microanalysis and analytical imaging of aluminum in biological samples. J.Trace Microprobe Tech. 16: 395-400.
27. Gandolfi L.,Stella M.P., Zambenedetti P. and Zatta P. (1998) Aluminum alters intracellular calcium homeostasis. Biochim. Biophys. Acta 1406: 315-320.
28. Zatta P. and Bordon L. (1998) Aluminum and biological systems. Proc. Int. Symp. on: Trace Elements in Human: New Perspectives, Morogianni, Athens, pp. 421-433.
29. Zambenedetti P., Giordano R. and Zatta P. (1998) Histochemical localization of glycoconjugates on microglial cells in Alzheimer's disease brain samples using Abrus precatorius, Maackia amurensis, Momordica charantia and Sambucus nigra lectins. Exper. Neurol. 153: 167-171.
30. Di Noto V., Dalla Via L. and Zatta P. (1999) Conformational studies of the trypsin-aluminum(III) complex in solution by Raman and Fourier transform infrared attenuated total reflectance spectroscopy. J. Raman Spectr. 30: 209-216
31. Messori L., Orioli P., Banholzer V., Pais I. and Zatta P. (1999) Formation of titanium(IV) transferrin by reaction of human serum apotransferrin with titanium complexes. FEBS Lett. 442: 157-161.
32. Di Noto V., Dalla Via L. and Zatta P. (1999) Conformational studies of the Trypsin-Aluminum(III) complex in solution by Raman and Fourier transform infrared attenuated total reflectance spectroscopy. J. Raman Spectr. 30: 209-216.
33. Suwalski M., Ungerer B., Villena F., Norris B., Cardenas H. and Zatta P. (1999) Interactions of Al(acac)3 with cell membranes and model phospholipid bilayers. J. Inorg. Biochem. 75: 263-268.
34. Zatta P., Zambenedetti P. and Milanese M. (1999) Activation of monoamine oxidase type-B by aluminum in rat brain homogenate. NeuroReport 10: 1-4.
35. Zatta P., Taylor A., Zambenedetti P., Milacic R., and Dell'Antone P. (1999) Aluminum inhibits the lysosomal proton pump from rat liver. Life Sciences 66: 2261-2266.
36. Zatta P., Lain E. and Cagnolini C. (2000) Effects of Aluminum on Activity of Krebs Cycle Enzymes and Glutamate Dehydrogenase in Rat Brain Homogenate. Eur. J. Biochem. 267: 3049-3055.
37. A.Toninello, G. Clari, M. Marcon, G.Tognon and P.Zatta (2000) Aluminum as an inducer of the mithocondrial permeability transition. J. Biol. Inorg. Chem. 5: 612-623.
37. Milanese M., M. Ibn lKayat and P.Zatta (2001) Inhibitory effect of aluminum upon dopamine b-hydroxylase from bovine adrenal gland. J. Trace Elem. Med.Biol. 15: 139-141.
38. Hidalgo J., Aschner M., Zatta P. and Vasak M. (2001) Roles of the metallothionein family of proteins in the central nervous system. Brain Res. Bull. 55: 133-146.
39. Mocchegiani E., Giacconi R., Cipriano C., Muzzioli M., Fattoretti P., Bertoni-Freddari C., Isani G., Zambenedetti P. and Zatta P. (2001) Zinc-bound metallothioneins as potential biological markers of ageing. Brain Res. Bull. 55: 147-156.
40. Suwalsky M., Ungerer B., Villena F., Norris B., Cardenas H. and Zatta P. (2001) Effects of AlCl3 on toad skin, human erythrocytes, and model cell membranes. Brain Res. Bull. 55: 205-210.
41. Zambenedetti P., Licastro F. and Zatta P (2002) Alzheimer's-like neuropathological features in the brain of rabbits food high cholesterol. J. Alzheimer's Disease 4(1) : 1-9.
42. Zatta P., Zambenedetti P., Giordano R., Wittkowski and Carpenè E. (2001) Localization of metallothioneins immunoreactivity in bovine pituitary gland. Life Sci. 70: 659-667.
43. Zatta P., Kiss T., Suwalsky M. and Berthon G. (2002) Aluminum as a promoter of cellular oxidation. Coord. Chem Rev. 228: 271-284.
44. Suwalsky M., Norris B., Kiss T. and Zatta P. (2002) Effects of Al(III) speciation on cell membranes and molecular models. Coord. Chem. Rev. 228:285-295 .
45. Di Noto V., Dalla Via L. and Zatta P. (2002) Binding approaches in the study of ligand-receptor interactions: detection of binding events in Al(III)-trypsyn and Al(III)-DL-DPPC liposomes systems. Coord. Chem. Rev. 228: 343-363.
46. Zatta P., Ibn lkhayat-Idrissi M., Zambenedetti P., Kilyen M. and Kiss T. (2002) Effects of the in vivo and in vitro treatment with aluminum(III) on the activity of mouse brain acetylcholinesterase. Brain Res. Bull. 6512: 1-5.
47. Zambenedetti P., Schmitt H.P., and Zatta P. (2002) Differential Distribution of degenerative and reactive astrocytes in Binswager's subcortical encephalopathy: Astroglial responses and metallothionein expression. J. Alzheimer's Dis.(In press)
PAPERS ON NATIONAL JOURNALS
1. Zatta P. and Zambenedetti P. (1995) Fisiopatologia dell'alluminio. Le Scienze. 325: 28-35.
2. Zatta P., Zambenedetti P. and Nicolini M. (1995) La chimica dell'alluminio e i sistemi biologici. La Chimica e l'Industria. 77: 797-802.
3. Andriani M., Nordio M., Zambenedetti P., Favarato M., Giordano R., Zatta P., and Saporiti E. (1995) L'alluminio: dalla storia alla ricerca. In: "L'emodialisi induce malattia?" (Saporiti E. and Marchini P., eds). Wichting Publ., Milano, Italy, pp. 9-21.
4. Nordio M., Gerotto M., Andriani M., Zambenedetti P. and Zatta P. (1995) Gli elementi in traccia nell'insufficienza renale cronica. In: L' "emodialisi induce malattia?" (Saporiti E. and Marchini P., eds). Wichting Publ., Milano, Italy, pp. 55-62.
REVIEWS/BOOK CHAPTERS/MONOGRAPHS
1. Banks W., Kastin A. and Zatta P. (1995) The blood-brain barrier in aluminum toxicity and Alzheimer's disease. In: Non neuronal cells in Alzheimer's disease (Zatta P. and Nicolini M., eds.) World Sci. Publ. Singapore, London, pp. 1-12.
2. Pizziuti A., Zambenedetti P. and Zatta P. (1995) La tossicita' dell'alluminio nell'ambiente acquatico. In: Argomenti di idrobiologia e acquacoltura. (Carpene' E., Isani G. and Serra R., eds.) CLEUB, Bologna, pp. 249-262.
3. Corain B., Bombi G.G., Tapparo A., Perazzolo M. and Zatta P. (1996)Aluminum toxicity and metal speciation: clear data and open questions. Coord. Chem. Rev. (Spec. issue) (Corain B., Zatta P., Bombi G.G. and Nicolini M., guest eds.) 149: 11-22.
4. Kiss T., Zatta P. and Corain B. (11996) Interaction of aluminum(III) with phosphate-binding sites: biological aspects and implications. Coord. Chem. Rev. (Spec. issue) (Corain B., Zatta P., Bombi G.G. and Nicolini M., guest eds.) 149: 329-346.
5. Harris W.R., Berthon G., Day J.P., Exley C., Flaten T., Forbes W.F., Kiss T., Orvig C. and Zatta P. (1997) Speciation of aluminum in biological systems. In: Research Issues in Aluminum Toxicology (Yokel R.A. and Golub M.S., eds.) Taylor and Francis, Washington D.C., pp. 91-116.
6. Lovell M.A., Ehmann W.D., Markesbery W.R., Melithil S., Swyt C.R. and Zatta P. (1997) Standardization in biological analyses of aluminum: What are the needs? In: Research Issues in Aluminum Toxicology (Yokel R.A. and Golub M.S., eds.) Taylor and Francis, Washington D.C., pp. 241-266.
7. Zatta P. and Zambenedetti P. (1997) Aluminum(III) speciation and biological effects: Implications in human and experimental toxicity. In: Cytotoxic. Mutagenic, and Carcinogenic Potential Heavy Metal Related to Human Environment. (Hadjiliadis N., ed) NATO ASI Series 2,, vol. 26, pp. 231-240.
8. Zatta P. and Zambenedetti P. (1997) Aluminum toxicity depends on the metal speciation. In: Aluminum Toxicity in Infants Hjealth and Disease.(Zatta P. and Alfrey A.C., eds.). World Sc. Publ., Singapore, London, pp. 40-53.
9. Zatta P., Giordano R. and Zambenedetti P. (1999) Glycosylation and microglial activation in Alzheimer's disease. In: Lectins and Pathology pp. 35-49. Seve A-P. and Caron M., eds. Harwood Acad. Publ. gmbh. Amsterdam, The Netherlands.
10. Zatta P., and Zambenedetti P. (1999) monoamine oxidase actvities on murine neuroblastoma cell upon acute or chronic treatment with aluminum or tacrine. Proceeding of the VI International Conference on Alzheimer's disease and related disorders pp. 613-619 (Iqbal K., Swaab C., Winblad B. and Wisniewski H., eds) J. Wiley and sons. Chichester, UK
11. Zatta P. e Zambenedetti P. (1999) Monoamine oxidase activities on murine neuroblastoma cells upon acute or chronic treatment with aluminum or tacrine. Proceedings of the VI International Conference on Alzheimer's disease and related disorders. (Iqbal K., Swaab C., Winblad B. and Wisniewski H., eds) J. Wiley and sons, Chichester, UK pp. 613-619.
12. Zatta P and Zambenedetti P. (1999) Lectins, microglia and Alzheimer's disease. In: Lectins and Pathology (M. Caron and A-P. Sève, eds) Hardwood Acad. Publ., Amsterdam, The Netherlands, pp. 35-49.
13. P.Zatta (2000) Aluminum neurotoxicity: Implications in Neurodegenerative Diseases. In : Metal Ions in Biology and Medicine (Centeno JA., Ph Collery, G. Vernet, RB Finkelman, H. Gibb and JC Etienne, eds) J. Libbey, Rome, Italy, vol. 6: 443-445.
14. P. Zatta and P. Zambenedetti (2000) Potential implications of aluminum in human pathology. In: Proceedings of the 2nd Intern. Symposium on Trace Elements in Human: "New Perspectives" (S.Ermidiou Pollet and S. Pollet, eds). G. Morogianni, Publ. Athens, Greece, pp741-751.
15. P.Zatta (2000) Aluminum and Health. Nutrition and Environment (United Nations-Sub-Committee on Nutrition) 21:33-34.
16. Zatta P. and M. Suwalsky. (2001) Aluminum, Membranes and Alzheimer's Disease. In: Aluminum and Alzheimer's Disease, C. Exley, (Editor), Elsevier, Amsterdam, pp. 279-291.
17. Suwalsky M., Villeda F., Norris B., Cardenas H., Zatta P. (2002) Interaction of metal ions with cell membranes and molecular models. In: Metal ions in Biology and Medicine. (Khassanova L., Maymard Ph, Khassanova J., Etienne C.J., Eds). J. Libbey Eutotext, Paris, pp. 119-122.
AUTHOR/EDITOR/COEDITOR OF BOOKS AND JOURNAL SPECIAL ISSUES
1. Nicolini M, Zatta P. and Corain B. (Eds) (1994) Aluminum in Chemistry, Biology and Medicine. Special issue. Life Chem. Rep. vol.149 pp 250
2. Corain B., Iqbal K., Nicolini M., Winblad B., Wisnioewski H., Zatta P. (1993) Alzheimer's disease: Advances in clinical and basic research. Wiley and sons. Chichester, pp. 633.
3. Nicolini M., Corain B., Zatta P. (1993) Alzheimer's disease and related disorders. Pergamon Press, Oxford, UK, pp. 474.
4. Nicolini M. and Zatta P. (1994) Glycobiology and the brain. Pergamon Press, Oxford, UK, pp 292.
5. Nicolini M, Zatta P. and Corain B. (Eds) (1994) Aluminum in Chemistry, Biology and Medicine: Clinical, Cellular, Molecular and Analytical Aspects of Aluminopathies. Life Chem. Rep. vol.149 pp 250
6. Zatta P. and Nicolini M. (eds) (1995) Non-neuronal cells in Alzheimer's disease. World Scientific, Singapore, London pp.232.
7. Zatta P. and Alfrey A.C. (1997) Aluminum Toxicity in Infants' Health and Disease. World Scientific, Singapore, London, pp. 245.
8. ZattaP. (2001) Metals and the brain. Brain Res. Bull. (Special issue) 55:
9. Zatta. (2002) Recent topics in aluminium chemistry. Coord. Chem. Rev. 228/2, pp. 394.
INTERNATIONAL CONFERENCE COMMUNICATIONS
1. Dell'Antone P., Bragadin M. and Zatta P. (1994) The accumulation of tacrine in acidic compartments of the cell. Intern. Conf.: Dementia in Parkinson's disease. Jerusalem, Israel, March 20-24. Behavioural Neurology 7: 11.
2. Bragadin M., Dell'Antone P., Palumbo M., and Zatta P. (1994) Tacrine accumulates in the ascidic cell compartments: potential therapeutics implications. IV Intern. Conf on Alzheimer's disease and related disorders. Minneapolis, MN, USA, July 29-August 3. Neurobiol. Aging 15: S1, p.421.
3. Bragadin M., Dell'Antone P., Palumbo M., and Zatta P. (1994) Effect of anticholinesterasic drugs on neublastoma cells and isolateds lysosomes. XVI Int. Conf. of Biochem. and Mol. Biology. New Delhi, India, Sept. 19-22, pP10, p.38.
4. Dell'Antone P., Bragadin M. and Zatta P. (1994) The accumulation of tacrine, amantadine and trihexylphenidyl in acidic compartments of the cell. XII Intern. Congr. of Pharmacology. Montreal, Canada, July 23-29, p.13.9.
5. Zatta P., Bragadin M., Zambenedetti P., and Dell'Antone P. (1994) Activationof acetylcholinesterase by aluminum. Intern. Conf. on Molecular Mechanisms of Enzyme Action. Bangalore, India, Sept. 23-25, P20.
6. Aimo E., Dell'Andrea E., Gambillara G., Martini G. Zambenedetti P. and Zatta P. (1996) Aluminum and Magnesium in Drinking water. Physiopatological aspects. Intern. Conf on Mineral Water and Soft Drinks. Florence, Italy, May 15-17, p. 63
7. Zatta P. and Zambenedetti P. (1996) Aluminum speciation and biological effects: implications in human and experimental toxicology. NATO ASI. Cytotoxic, Mutagenic and Carcinogenic Potential of Heavy Metals Related to Human Environment. Przesieka, Poland, June 15-26. p. 107-108.
8. Zambenedetti P. and Zatta P. (1996) Al(III) speciation and cell pathology. NATO ASI. Cytotoxic, Mutagenic and Carcinogenic Potential of Heavy Metals Related to Human Environment. Przesieka, Poland, June 15-26. p. 228-229.
9. Zatta P. and Zambenedetti P. (1997) The relevance of Al(III) speciation in the modulation of the activity of acetylcholinesterase, Na+/K+-ATPase, carbonic anhydrases and hexokinase. Int. Conf. on Aluminum and Silicon in Biology. Keele University, UK, February 24-26.
10. Zatta P. and Zambenedetti P. (1997) Aluminum and biological systems: effects on lysosomes. Intern. Symp. on Trace Elements in Humans: New Perspectives. Athens, Greece, October 9-11, P.L.2.
11. Zatta P., Giordano R. and Zambenedetti P. (1998) Metallothioneins are highly expressed in the astrocytes from Alzheimer's disease brain. VI Intern. Conf. on Alzheimer's disease and Related Disorders. Amsterdam NL, July 18-23. Neurobiol. Aging S50, p209.
12. Zatta P. and Zambenedetti P. (1998) Effects of aluminum or tacrine on enzymatic activities of MAO A and B in neuroblastoma cells. VI Intern. Conf. on Alzheimer's disease and Related Disorders. Amsterdam NL, July 18-23. Neurobiol. Aging S118, p500.
13. Zatta P. (1998)Al(III) Aluminum speciation and some biological effects on specific subcellular targets. COST D8 and ESF Workshop on Biological and Medicinal Aspects of Metal Ion Speciation. K24, University JATE, Szeged, Hunharym August 23-25.
14. Zatta P., Dell'Antone P., and Zambenedetti P. (1998) Anticholinesterasic drugs: tacrine, not physostigmine accumulates in intracellular acidic vesicles. VII Congr. of Mediterranean Soc.of Clinical Pharmacology. Marrakech, October 28-30, C6.
15. Zatta and P. Zambenedetti (1999) Aluminum speciation and biological effects: Potential implications in human pathology. 5th Intern. Symp. on Applied Bioinorganic Chemistry. Corfù, Greece, April 13-17 p. 205.
16.M Andriani, M. Nordio and P. Zatta (1999) ACE Inhibitors (ACE-I) and angiotensin- II receptors antagonists (Ang II) in kidney protection. I Intern. Congr. on Hypertension: From physiopathology to treatment. Fes, Moroccco, 28-30 October.
17. P. Zatta and P. Zambenedetti (1999) Aluminum neurotoxicity: implications in neurodegenerative diseases. 2nd Intern. Symp. on Trace Elements in Human: New Perspectives. Athens, Greece 7-9 October, P.P.47.
18 P. Zambenedetti and P.Zatta (2000) Espressione delle metallotioneine nel cervello di mammiferi. VI Nat. Conf. A.I?S.E.T.O.V. Siena, Italy 17-19 February, pp.
19. P.Zatta (2000) Aluminum neurotoxicity: implications in neurodegenerative diseases. 6th Intern. Symp. on Metal ions in Biology and Medicine. Puerto Rico, 7-10 May.
20. P.Zatta (2000) Aluminum Neurotoxicity: Implications in Some Neurodegenerative Diseases. VI Intern. Symp. on Metal Ions in Biology and Medicine. San Juan, Puerto Rico, 7-10 May, PL110.
21. P.Zatta, M.Andriani, P. Zambenedetti (2000) Histopathological findings in the brain of uremic patients in dialysis. First International Conference on Metals and the Brain: From Neurochemistry to Neurodegeneration. Padova 20-23 September 2000. J. Alzheimer's Disease vol.2, n.3-4: S1/17.
22.E. Moccheggiani, R. Giacconi, C.Cipriano, M.Muzzioli, C. Bertono-Freddari, P.Fattoretti, E. Carpené and P. Zatta. (2000) Metallothioneins as possible markers pf ageing. First International Conference on Metals and the Brain: From Neurochemistry to Neurodegeneration Padova 20-23 September 2000. J. Alzheimer's Disease vol.2, n.3-4: S2/2.
23. M. IbnLkayat P. Mazzei and P.Zatta (2000) In vivo and in vitro effects of Aluminum on acetylcholinesterase. First International Conference on Metals and the Brain: From Neurochemistry to Neurodegeneration Padova 20-23 September 2000. J. Alzheimer's Disease vol.2, n.3-4: S6/9.
24. P. Zambenedetti, E. Rossipal, E. Karpf, R. Kleinert and P. Zatta (2000) Expression of metallothionein I+II during human brain development. First International Conference on Metals and the Brain: From Neurochemistry to Neurodegeneration. Padova 20-23 September 2000. J. Alzheimer's Disease vol.2, n.3-4: P7.
25. E. Carpené, P. Zambenedetti, G. Isani, W. Wittkowski and P. Zatta (2000) Presence of metallothioneins in bovine hypophysis. First International Conference on Metals and the Brain: From Neurochemistry to Neurodegeneration. Padova 20-23 September 2000. J. Alzheimer's Disease vol.2, n.3-4: P22.
26. Zatta P. and Zambenedetti P. (2001) Metallothionein I-II in the developing human brain. SONA: 5 th Soc. Neurosc. Africa Intern. Conf. Nairobi, Kenya 23-27 April. #65.
27. Polec K., Szpunar J. Lobinski R. P. Zambenedetti and P. Zatta (2001) Investigation of aluminum binding by neuroblastoma cells by hyphenated techniques. I Intern. Conf. FESTEM, Venice, Italy P.3.14.
28.Zatta P., Rossipal E., Karpf E., Kleinert R., and Zambenedetti P. (2001) Expression of metallothioneion I-II in the human brain. I Intern. Conf. FESTEM, Venice, Italy P.3.14.
29.P.Zatta and P. Zambenedetti (2001) Metallothioneins-I-II expression in some human neurodegenerative disorders, XIV Int. Congr. Polish Pharmacol. Soc. Krakow 10-13 September, pp. 82-83.
30.P.Zambenedetti, E.Rossipal, R.Kleinert, E.Karpf, P.Zatta, (2001) Metallothionein I-II in the human brain. 3rd Intern. Sympos. On Trace Elements in Humans: New Perspectives. Athens 4-6 October, pp- 75.
31.M.Suwalsky, B.Ungerer, B.Norris, F.Villena, H.Cardenas, F.Cuevas, C.P.Sotomayor and P.Zatta (2001) Interaccion del aluminio(III) con bicapas lipidicas y su relacion con la infermedad de Alzheimer. XXIV Jornadas Chilenas de Quimica, Temuco, Cile, 28-30 Noviembre.
32. M. Suwalsky, F. Villena, H. Cardenas, B. Norris, C.P. Sotomayor and P.Zatta (2002) Estudios estructurales y funcionales de membranas cellulares. 10 Encuendro de Investigaciones de la Universidad de Concepcion, Concepcion, Cile, 7 y 8 de enero.
33. P. Zatta and P. Zambenedetti (2002) Biological and Biochemical properties of Ti(IV). 10th International Conference on Trace Elements. Budapest, 3-7 July.
34. P. Zatta, C. Di Pisa, M. Beltramini, P. Zambenedetti (2002) Expression of metallothioneins and astrocytosis in the brain of mice submitted to physical or chemical stress. II Intern. Conf. On Metals and the Brain: From Neurochemistry to Neurodegeneration. Fez, Morocco 24- 28 Sept., Abstract pp. 33.
35. M. Suwalsky, C. Schneider, H. cardenas, B. Norris, F. Cuevas, C.P. Sotomayor, P. Zatta (2002) Interaction of Pb(II) ions with cell membranes and molecular models. II Intern. Conf. On Metals and the Brain: From Neurochemistry to Neurodegeneration. Fez, Morocco 24- 28 Sept., Abstract pp. 29.
NATIONAL CONFERENCE COMMUNICATIONS
1. Zatta P., Zambenedetti P. and Corain B. (1994) Rilevanza della speciazione del metallo sull'interazione tra alluminio(III) e sistemi biologici. V Natl. Conf.: Interazione di metalli e loro composti com biomolecole. S.Agnello, April 7-9, p.45.
2. Zatta P. and Zambenedetti P. (1994) The relevance of the metal speciation on the interaction between aluminum anf biologiccal systems. III Natl. Conf. AISETOV. Modena, October 28-29, p.47.
3. Zatta P. and Zambenedetti P. (1995) Attivazione dell'acetilcolinesterasica da parte dell'alluminio. Natl. Conf of Italian Neuroscience Soc..on Modelli Sperimentali in Neurologia e Psichiatria. Bosisio Parini, Italy, October 15.C7.
4. Zatta P. (1996) Aspetti storici ed attuali sull'impiego del magnesio in terapia. Natl. Conf on Il Magnesio: Aspetti biochimici e chimico clinici. Padova, Italy, October 26, p. 3-5.
5. Zatta P. (1996) Aspetti fisiopatologici nell'ipomagnesemia dell'anziano. IX Natl. Conf of Italian Biologists Soc.: Alimenti, Nutrizione e Cosmetici. Grado, Italy, October 10-13, p. 33-34.
6. Zatta P. (1996) Aspetti storici ed attuali sull'impiego del magnesio in terapia. Natl. Conf.: Il Magnesio-Aspetti Biochimici e Clinici. University of Padova, October 26, p. 3-5.
7. Toninello A. and Zatta P. (1997) Effect of aluminum on permeability transition of liver mitochondria. XLII Natl. Congr. Italian Biochemical Soc.. Joint Symposia. Israel Soc. for Biochemistry anD Molec. Biol. and Italian Soc. Exp. Biol. Ancona, Italy, p. 247.
8. Zambenedetti P. and Zatta P. (1998) Metallothioneins overexpression in astrocytes of Alzheimer's disease subjects. V Natl Congr. AISETOV, Bologna, Italy September 26.
DOCTORAL DISSERTATIONS
1994
1. Marturano B.: Effects of tacrine on murine neuroblastoma cells. Faculty of Pharmaceutical Sciences, University of Padova.
2. Bruno V. Chemical and biological models for the study of aluminum toxicity: The relevance of metal speciation. University of Padova, Department of Biology.
1995
1. Cagnolini C. Effects of aluminum on some emzymatic systems. Faculty of Pharmaceutical Sciences, University of Padova.
2. Cavalieri C. Tin neurotoxicity. Faculty of Pharmaceutical Sciences, University of Padova.
3. Coppola A. Utilization of magnesium in cytophylaxis. Faculty of Pharmaceutical Sciences, University of Padova.
1996
1. Tullio S. Physiopathological aspects of magnesium in urology and nephrology. Faculty of Pharmaceutical Sciences, University of Padova.
2. Gandolfi L. Effects of aluminum on intracellular calcium metabolism. Faculty of Pharmaceutical Sciences, University of Padova.
3. Bordon L. Effects of aluminum on the activity of some lysonal enzymes. University of Padova, Department of Biology.
4. Chimenton A. Effect of aluminum on ematic cells. Faculty of Pharmaceutical Sciences, University of Padova.
5. Nicosia V. Biological effects ofaluminum and tacrine on neuroblastoma cells. Faculty of Pharmaceutical Sciences, University of Padova.
1997
1. Mason P. Toxicological aspects of aluminum in pediatry. Faculty of Pharmaceutical Sciences, University of Padova.
2. Zannini G. Prooxidant effect of aluminum on human lymphocytes and on neuroblastoma cells. Faculty of Pharmaceutical Sciences, University of Padova.
1998
1. Sartori L. Physiopathological and pharmacological aspects of magnesium
in migraines. Faculty of Pharmaceutical Sciences, University of Padova.
2. Milanese M. Some biological model for the study of the overaccumulation
of iron and aluminum in Parkinson's disease Faculty of Pharmaceutical Sciences,
University of Padova.
1999
1. Stefania Rosan. Biological models for the study of some pharmacological aspects of melatonin: Possibile implication in some neurodegenerative disorders. Faculty of Pharmacological Sciences
2. Aurelio Garofano. Biochemical effects of aluminum on human platelets.Possibile implication in some neurodegenerative disorders . Faculty of Pharmacological Sciences
3. Enzo Lain. Biochemical and Biophysical models for the study of aluminum neurotoxicity. Faculty of Pharmacological Sciences
2001
1. Paolo Carampin. In vivo and in vitro biochemical properties of melatonin Faculty of Pharmacological Sciences
2002
1. Cristina Di Pisa. In vitro studies on the biochemical properties of metallothioneins. Faculty of Biological Sciences.
2. Elena Zattoni. Chemical and biochemical properties of Titanium (IV). Faculty of Pharmacological Sciences
CONGRESS ORGANIZATION
1992. III Int. Conf. On Alzheimer's Disease and Related Disorders. Padova.
1994. International wokshop on Aluminum in Chemistry, Biology and Medicine, Abano terme, Italy.
1996. Il Magnesio: Aspetti Biochimici e Clinici. University of Padova, Italy.
2000. I Intern. Conf. On Metals and the Brain: From Neurochemistry to Neurodegeneration. Padova.
2002. I Intern. Conf. On Metals and the Brain: From Neurochemistry to Neurodegeneration. Fez, Marocco.
TEACHING
1994-presently
"Professore a contratto", University of Padova, Faculty of Medicine, Post-graduate School on Chemistry and Biochemical Chemistry.
VISITING SCIENTIST
1996. University of Surrey, Guilford, UK, Robens Institute.
1998-2000. Department of Biochemsitry, University of Georgia, Athens
(GA) USA
2000 and 2002. Department of Biotechnologies. Tel Aviv. Israele
2001 and 2002. Faculty of Chemical Sciences. Concepcion. Cile
INTERNATIONAL PROJECTS
1994-1996. CNR Bilateral Projects Lectins Biochemistry (Prof. R. Cummings and R.D. Smith, University of Georgia, USA)
1997-1999. CNR Bilateral Projects Aluminum neurotoxicology (Dr Andrew Taylor, University of Surrey, Guilford, UK)
1998-2001. Coordinator of a CEE, COST project on Interdisciplinary Aspects of Aluminum Speciation and Biological effects. (Prof. Tamas Kiss, University of Szeged, Hungary; Dr Guy Berthon, CNRS. France; Dr R.Lobinsi, CNRS, Pau, France; Dr R. Milacic, Josef Stefan Institute, Ljubljana, Slovenia; Prof. P. Rubini, University of Nancy, France; Dr C. Exley, Keele University, UK).
2000-2002. Department of Biotechnologies. Israele
2000-2002. Faculty of Chemical Sciences. Cile
NATIONAL PROJECTS
1994. Eli Lilly- Preclinical studies on Tacrine
1995-1996. Park Davies: Studies on Tacrine in vivo and in vitro
1995-96. Regione Veneto (Alpe-Adria) Health Projects on Aluminum Neurotoxicity in Uremic Subjects in Hemodialysis
1997-98. Regione Veneto Health Projects for the Constitution of the first Italian Brain Bank.
1999-2002. WHO and Regione Veneto. Neurotossicologia degli Emodializzati in Marocco
For further information:
Prof. Paolo Zatta
CNR-Institute for Biomedical Technologies
Padova Unit on Metalloproteins
University of Padova
Department of Biology
Via G. Colombo 3,
35121 Padova, Italy
Fax +39 049 8276330
Tel +39 049 8276331
Mail to zatta@mail.bio.unipd.it
Aluminum International
Network http://www.bio.unipd.it/~zatta/aluminum.html
