Inorganic Chemistry Seminar: Professor Luigi Casella, University of Pavia (Host: Dan Stack)
Inorganic Chemistry Seminar: Professor Luigi Casella, University of Pavia (Host: Dan Stack)
About the Seminar
"Metal ions, dopamine, and oxidative stress in neurodegenerative diseases"
Growing evidence supports the view that disruption of metal homeostasis in the brain is linked to neurodegenerative diseases such as Alzheimer and Parkinson's diseases. Toxic effects of metal ions such as iron and copper may be directly associated with the possibility to promote and stabilize oligomers of neuronal peptides, but in most cases these effects depend on the redox properties of metal ions and the production of reactive oxygen species (ROS). In particular, the interaction of these ions with neuronal peptides has an influence on: (i) the metal redox potential and hence their reactivity towards dioxygen or hydrogen peroxide, which leads to ROS production, (ii) the ability to promote oxidation of reactive catecholamine neurotransmitters present in the brain, and (iii) the post-translational modifications of the endogenous peptides and their aggregation properites. It is therefore of extreme importance to clarify to which extent and in which conditions (e.g. solution vs. membrane environment) the interaction of metal ions with neuronal peptides has pro-oxidant effects.
Recent research in our group focused on a systematic investigation of the binding and reactivity of copper and iron ions (both heme and non-heme) with peptide fragments of b-amyloid (Ab), a-synuclein (aS), tau protein (Rnt), and prion protein (PrP), containing the residues which act as binding sites for the metal ions. Neuronal toxicity of ferric heme is particularly relevant under conditions of heavy heme release occurring, e.g. on traumatic brain injury. More generally, toxic effects of trace metal ions become significant when their reactivity is prolonged for extended periods of times, resulting in chronic neuronal inflammation.
About the Speaker
Luigi Casella graduated in Chemistry cum laude at the University of Milano (Italy) in 1973, and then he served as a Navy officer until 1975. In the period 1978-1979, he did postdoctoral work with professor James A. Ibers at the Department of Chemistry, Northwestern University, Evanston, IL (U.S.A.). He became assistant professor (1977) and, subsequently, associate professor (1983-1990) at the University of Milano. In 1990, he moved to the University of Pavia, where he was appointed as full professor of General and Inorganic Chemistry.
He has been the project coordinator of several networks of national and European research teams. In particular, at the European level, he was the coordinator of a Human Capital and Mobility program on "Dinuclear and polynuclear metal centres in biology: enzymes and synthetic analogues", an INTAS project on "The basic chemistry of peroxynitrite and related species: reactions with antioxidants, metalloproteins and their models", and the Chairman of the European COST Chemistry Action D21 "Metalloenzymes and chemical biomimetics", involving more than 100 laboratories.
He is the author of more than 240 papers in international chemical and biochemical journals, and an international patent. He has been the editor with F. Montanari of the book “Metalloporphyrins catalyzed oxidations", by Kluwer (Dordrecht, 1994) and the Editor of Volume 6 “Homogeneous catalytic applications” of the series “Comprehensive Inorganic Chemistry 2” by Elsevier (2013), with Jan Reedijk and Kenneth Poeppelmeier Chief Editors.
His primary scientific interest has been in biological oxidation reactions. In particular, he was interested in the processes promoted by proteins and enzymes containing heme prosthetic groups or copper centers associated in dinuclear or polynuclear clusters. The approach typically involved parallel studies on the metal enzymes and on suitable active site model coordination compounds. More recently, he addressed increasing research efforts by his group toward the understanding of the molecular basis of human pathologies, in particular neurodegenerative diseases, since they often involve induction of oxidative processes by metal ions that produce damage to key cellular components. He is a member of the Editorial Board of a number of scientific Journals, and is the author of more than 240 papers in international chemical and biochemical journals, and an international patent. He has been the editor with F. Montanari of the book “Metalloporphyrins catalyzed oxidations", by Kluwer (Dordrecht, 1994) and the Editor of Volume 6 “Homogeneous catalytic applications” of the series “Comprehensive Inorganic Chemistry 2” by Elsevier (2013), with Jan Reedijk and Kenneth Poeppelmeier Chief Editors.
He has been the founder of Noxamet Ltd, an academic spin-off company that aims at promoting pharmacological applications of a new class of metal-based nitric oxide donor molecules.