Department of Structural and Functional Biology
Via Alberto da Giussano 12
21052 Busto Arsizio (VA)
Mauro Fasano graduated
in Chemistry with honors in 1989 and earned his Ph.D. in Chemical
Sciences in 1992, both from the University of Torino, Italy. From
1992 to 2000 was appointed to a position of Assistant Professor
of Chemistry at the School of Sciences of the University of Torino.
From 2000 to present he is Associate Professor of Biochemistry at
the School of Sciences of the University of Insubria.
Since 1998 he has supervised the Biochemistry and Proteomics unit
of the Bioindustry Park Canavese, a EU biotechnology exploitation
He is member of the Italian Chemical Society, of the Italian Society
of Biochemistry and Molecular Biology, of the League against Parkinson’s
Disease, of the Italian section of the Human Proteome Organization.
He acts as a reviewer for the following journals: Journal of Inorganic
biochemistry, Journal of Magnetic Resonance, Biochimica Biophysica
Acta, European Journal of Biochemistry (now FEBS Journal), Journal
of Pharmacy and Pharmacology, Progress in Neurobiology, Proteomics,
Journal of Neurochemistry.
He is author of 70 papers on peer-reviewed journals and of some
contributions to edited books and encyclopedias.
Qualifications and awards
|Vice-president of the Italian
NMR discussion group.
President-elect of the life science division of the Italian Chemical
Member of the scientific board of the Proteome Chemistry discussion
group of the Italian Chemical Society.
|1. Applications of 1H-NMR
relaxometry in the investigation of heme-human serum albumin
2 . Human serum albumin (HSA), the most prominent protein in plasma,
is best known for its exceptional ligand binding capacity. For many
compounds, HSA provides a depot so they will be available in quantities
well beyond their solubility in plasma. Moreover, HSA abundance (its
concentration being 45 mg/mL, in the serum of human adults) makes
it an important determinant of the pharmacokinetic behavior of many
drugs. Among hydrophobic molecules, heme binding to HSA is of peculiar
relevance for the heme iron reuptake following hemolytic events. Heme
binding to HSA endows the protein with peculiar spectroscopic properties.
Electronic absorption and relaxometric data indicate the occurrence
of a high-spin Fe(III) center with no water in the inner coordination
sphere, and the occurrence of a strong contribution from a cluster
of water molecules buried nearby. This second-sphere contribution
may be employed as a structure-dependent spectroscopic observable
to follow a number of events involving the conformation of the protein.
Among them, allosteric equilibria are investigated upon heterotropic
interaction of drugs with primary transport sites of the protein.
More recently, we investigated the effect of fatty acid binding to
the N and B conformational states of Mn(III)heme-HSA (i.e., at pH
7.0 and 10.0, respectively) by optical absorbance and NMR spectroscopy.
Myristate binding to a secondary site (FAx), allosterically coupled
to the heme site, not only increases optical absorbance of Mn(III)heme-bound
HSA by a factor of 3, but also increases the Mn(III)heme affinity
for the fatty acid binding site FA1 by 10-500-fold. Cooperative binding
appears to occur at FAx and accessory myristate binding sites.
3 . Differential protein expression in Parkinson’s Disease.
4 . Parkinson’s disease (PD) is the second most common neurodegenerative
disorder after Alzheimer’s disease (AD), with a prevalence of
2-3% among people over the age of 65 years. The characteristic motor
symptoms are associated with the depletion of dopaminergic melanin-containing
neurons in the substantia nigra pars compacta (SNpc) and a consequent
loss of dopamine in the striatum. Another important pathological feature
is the presence, especially in SNpc neurons, of eosinophilic cytoplasmic
inclusion bodies (Lewy bodies). Lewy bodies show a strong staining
with anti- α -synucleins antibodies, a presynaptic protein involved
in a familial form of the disease. In vitro studies showed that both
mutated and wild type a -synucleins do form fibrils similar to those
of Lewy bodies; moreover, α -synucleins molecules carrying either one
of the three point mutations observed in the familial PD will aggregate
faster than the wild type protein.
5. We performed a two-dimensional electrophoretic (2DE) separation
of proteins extracted from ex vivo substantia nigra specimens from
controls and PD patients. Forty-one proteins have been identified
by peptide mass fingerprinting and their expression levels have been
compared. Among them, nine proteins show differential expression in
6. We have considered the effect of dopamine and of pro- and anti-oxidant
factors on viability of a dopaminergic cell line (SH-SY5Y human neuroblastoma).
Extracellular contribution to dopamine cell toxicity is ruled out
by adding catalase that removes hydrogen peroxide formed by spontaneous
dopamine oxidation. Cell death is reduced by 75% in the presence of
catalase, and appears to be dose-dependent. Cu(II) ions appear to
be a moderate determinant of reactive oxigen species, whereas the
simultaneous presence of Cu(II) and glutathione leads to the occurrence
of Cu(I)-catalysed Haber-Weiss cycle with a consequent decrease of
cell viability. Expression of increased levels of wild-type alphα -synucleins through transfection of the cell line determines a cytoprotective
effect. Transfected cells are more resistant to oxidative insults,
whereas cells transfected with a control vector are not.
|Mauro Fasano is teaching
Biochemistry and Biochemical Methods in the undergraduate courses
of Biology, Health Biology, and Biotechnology. In the graduate course
of Biology applied to Biomedical Research he is teaching biochemistry
modules in the courses of Experimental Biology, Basic Neuroscience
and Physiopathology of the immune system, and Proteomics in the graduate
course of Biology.
Vice-director of the Department of Structural and Functional Biology.
Scientific secretary of the Centre of Neuroscience.
Director of the Master in Bioinformatics.
Member of the Board of the doctorate school of cellular and molecular
Coordinator of the School Commission for Tutorial Activities.
|1. P. Ascenzi, M. Colasanti,
M. Fasano, A. Bertollini, “Stabilization of the T-state of human
hemoglobin by proflavine, an antiseptic drug”, Biochem. Mol.
Biol. Int., 47, 991-995 (1999).
2. S. Aime, B. Bergamasco, M. Casu, G. Digilio, M. Fasano, S. Giraudo,
L. Lopiano, “Isolation and 13C-NMR characterization of an insoluble
proteinaceous fraction from substantia nigra of patients with Parkinson’s
Disease”, Mov. Disord. 15, 977-81 (2000).
3. L. Lopiano, M. Chiesa, G. Digilio, S. Giraudo, B. Bergamasco, E.
Torre, M. Fasano, “Q-band EPR investigations of neuromelanin
in control and Parkinson’s disease patients”, Biochim.
Biophys. Acta, 1500, 306-312 (2000).
4. L. Lopiano, M. Fasano, S. Giraudo, G. Digilio, B. Bergamasco, E.
Torre, S. H. Koenig, S. Aime, “Nuclear Magnetic Relaxation Dispersion
profiles of Substantia Nigra pars compacta in Parkinson’s disease
patients are consistent with protein aggregation”, Neurochem.
Int. 37, 331-336 (2000).
5. M. Sette, M. Bozzi, A. Battistoni, M. Fasano, M. Paci, G. Rotilio,
“Investigation of the active site of Escherichia coli Cu,Zn
superoxide dismutase reveals the absence of the copper-coordinated
water molecule. Is the water molecule really necessary for the enzymatic
mechanism?”, FEBS Lett. 483, 21-26 (2000).
6. M. Mattu, A. Vannini, M. Coletta, M. Fasano, P. Ascenzi. “Effect
of Bezafibrate and Clofibrate on the Heme-Iron Geometry of Ferrous
Nitrosylated Human Serum Heme-Albumin: An EPR Study.”, J. Inorg.
Biochem. 84, 293-296 (2001).
7. M. Fasano, S. Baroni, A. Vannini, P. Ascenzi, S. Aime, “Relaxometric
investigations of human hemalbumin”, J. Biol. Inorg. Chem. 6,
8. S. Baroni, M. Mattu, A. Vannini, R. Cipollone, S. Aime, P. Ascenzi,
M. Fasano, “Effect of ibuprofen and warfarin on the allosteric
properties of haem-human serum albumin. A spectroscopic study.”
Eur. J. Biochem. 268, 6214-6220 (2001).
9. P. Ascenzi, M. Fasano, M. Marino, G. Venturini, R. Federico, “Agmatine
oxidation by copper amine oxidase: biosynthesis and biochemical characterization
of N-amidino-2-hydroxypyrrolidine”, Eur. J. Biochem. 269, 884-892
10. F. Bolzoni, S. Giraudo, B. Bergamasco, L. Lopiano, M. Fasano,
P.R. Crippa, “Magnetic investigations of human mesencephalic
neuromelanin” Biochim. Biophys. Acta 1586, 210-218 (2002).
11. M. Fasano, M. Mattu, M. Coletta, P. Ascenzi, “The heme-iron
geometry of ferrous nitrosylated heme-serum lipoproteins, hemopexin,
and albumin: a comparative EPR study”, J. Inorg. Biochem. 91,
12. P. Ascenzi, M. Fasano, L. Gradoni, “Do hemoglobin and hemocyanin
impair Schistosoma killing by NO?”, IUBMB Life 53, 287-288 (2002).
13. D. Delli Castelli, E. Lovera, P. Ascenzi, M. Fasano, “Unfolding
of the loggerhead sea turtle (Caretta caretta) myoglobin: A 1H-NMR
and electronic absorbance study”. Protein Sci. 11, 2273-2278
14. E. Monzani, M. Curto, M. Galliano, L. Minchiotti, S. Aime, S.
Baroni, M. Fasano, A. Amoresano, A. M. Salzano, P. Pucci, L. Casella,
“Binding and Relaxometric Properties of Heme Complexes with
Cyanogen Bromide Fragments of Human Serum Albumin”, Biophys.
J. 83, 2248-2258 (2002).
15. M. Mattu, M. Fasano, A. Spallarossa, M. Bolognesi, P. Ascenzi,
“Hemopexin – The primary specific carrier of plasma heme”
, Biochem. Mol. Biol. Educ. 30, 332-335 (2002).
16. M. Fasano, S. Giraudo, S. Coha, B. Bergamasco, L. Lopiano, “Residual
substantia nigra neuromelanin in Parkinson’s disease is cross-linked
to α -synucleins”. Neurochem. Int. 42, 603-606 (2003).
17. M. Fasano, S. Baroni, S. Aime, M. Mattu, P. Ascenzi, “Determination
of ferric heme-human serum albumin by 1H-NMR relaxometry”. J.
Inorg. Biochem. 95, 64-67 (2003).
18. M. Fasano, M. Orsale, S. Melino, E. Nicolai, F. Forlani, N. Rosato,
D. Cicero, S. Pagani, M. Paci, “Surface changes and role of
buried water molecules during the sulfane sulfur transfer in Rhodanese
from Azotobacter vinelandii: a fluorescence quenching, 15N NMR relaxation,
and nuclear magnetic relaxation dispersion spectroscopic study”.
Biochemistry 42, 8550-8557 (2003).
19. S. Aime, G. Digilio, E. Bruno, V. Mainero, S. Baroni, M. Fasano,
“Modulation of the antioxidant activity of HO scavengers by
albumin binding: a 19F-NMR study”. Biochem. Biophys. Res. Commun.
307, 962–966 (2003).
20. M. Basso, S. Giraudo, L. Lopiano, B. Bergamasco, E. Bosticco,
A. Cinquepalmi, M. Fasano. Proteome analysis of mesencephalic tissues:
evidence for Parkinson’s disease. Neurol. Sci. 24, 155-156 (2003).
21. D. Corpillo, G. Gardini, A. M. Vaira, M. Basso, S. Aime, G. P.
Accotto, M. Fasano, “Proteomics as a tool to assess substantial
equivalence of genetically modified organisms: the case of a virus-resistant
tomato”. Proteomics, 4, 193-200 (2004).
22. M. Fasano, G. Fanali, F. Polticelli, P. Ascenzi, G. Antonini,
“1H-NMR relaxometric characterization of bovine lactoferrin”.
J. Inorg. Biochem., 98, 1421-1426 (2004).
23. M. Fasano, A. Bocedi, M. Mattu, M. Coletta, P. Ascenzi “Nitrosylation
of rabbit ferrous heme-hemopexin”. J. Biol. Inorg. Chem., 9,
24. M. Basso, S. Giraudo, D. Corpillo, B. Bergamasco, L. Lopiano,
M. Fasano, “Proteome analysis of human substantia nigra in Parkinson’s
disease”. Proteomics, 4, 3943-3952 (2004).
25. A. Bocedi, S. Notari, A. Bolli, M. Fasano, P. Ascenzi, “Binding
of anti-HIV drugs to human serum albumin”. IUBMB Life, 56, 609-614
26. M. Bisaglia, I. Tessari, L. Pinato, M. Bellanda, S. Giraudo, M.
Fasano, E. Bergantino, L. Bubacco, S. Mammi, “A topological
model of the interaction between alphα -synucleinsand sodium dodecyl
sulfate micelles”. Biochemistry, 44, 329-339 (2005).
27. P. Ascenzi, A. Bocedi, M. Fasano, M. Gioia, S. Marini, M. Coletta,
“Proton-linked subunit heterogeneity in ferrous nitrosylated
human adult hemoglobin: an EPR study”. J. Inorg. Biochem., 99,
28. P. Ascenzi, A. Bocedi, A. Bolli, M. Fasano, S. Notari, F. Polticelli,
“Allosteric modulation of monomeric proteins”. Biochem.
Mol. Biol. Educ., 33, 169-176 (2005).
29. P. Ascenzi, A. Bocedi, S. Notari, E. Menegatti, M. Fasano, “Heme
impairs allosterically drug binding to human serum albumin Sudlow's
site I”. Biochem. Biophys. Res. Commun., 334, 481-486 (2005).
30. G. Fanali, R. Fesce, C. Agrati, P. Ascenzi, M. Fasano, “Allosteric
modulation of myristate and Mn(III)heme binding to human serum albumin
– Optical and NMR spectroscopy characterization”. FEBS
J., 272, 4672-4683 (2005).