Studies of biochemistry and physiopathology of metalloproteins

Paolo Zatta (Manager of the Unit) Fernanda Ricchelli (Senior Researcher); Staff members: Ennio Carbone, Daniele Cervellin, Silvano Gobbo, Paolo Rocco, Giuseppe Tognon, Antonio Cervellin.
The aim of the Unit is the study on the role of metal ions on different pathologies. This unit is comprehensive of two laboratories involved in the following issues.
A) Role of metal ions in human and experimental neurophysiopathology. (
Interest in the physiological role of metal ions has revived in recent years. The study of metal ions, which is highly interdisciplinary, used to be, and still is to some extent, mainly the domain of bioinorganic chemistry and occupational-environmental medicine. However, the study of the physiopathology of metal ions extends far beyond these fields, promoting contact and exchanges between disciplines ranging from the biomedical to the chemical and physical sciences. This laboratory is deeply involved to better understand the role played by metal ions in relevant human neuropathologies (e.g., Alzheimer's disease, Parkinson's disease and other); the search for new biomarkers useful to the diagnosis of these devasting diseases; the study on the role of metal ions in the aggregation and fibrillogenesis of the b-amyloid; the study of pharmacological products that could avoid Alzheimer's disease plaque formation in the brain; and the study of new pharmacological products for the chelation therapy.
B)Photosensitization processes in biological
Photosensitization is a process induced by highly toxic, reactive oxygen species (ROS), produced after irradiation by UV-visible light of many fluorescent molecules (in particular, porphyrins and analogous compounds, such as phthalocyanines, naphthalocyanines etc. and some of their metal-derivatives) that is involved in cell damage and death. The photosensitization process can be highly noxious and cause irreversible cell damages, as observed in human porphyria or in skin lesions such as erythema and cancer. However, porphyrins and other photosensitizers have found useful biomedical applications in the treatment of several diseases, as, for ex., in the photodynamic therapy of tumors (PDT) and in the destruction of atheromatous plaques and psoriatic lesions. Pioneering studies concern the use of photosensitizing molecules as antibacterial and antiviral agents. On these basis, it is obvious an increasing interest in identifying critical mechanisms of cell killing and understanding the bases for effective photosensitizers. The existence of multiple cellular targets (citoplasmic membranes, mitochondria, lysosomes, endoplasmic reticulum) makes it difficult to distinguish the critical events leading to cell death from PDT. However, with more sensitive techniques to detect photosensitizer localisation and proper molecular and biochemical strategies to map cellular events during and after photosensitization, some important results emerged in the last years. The subcellular localisation of many photosensitizers and the early responses to light activation indicate that mitochondria play a major role in photodynamic cell death. Many photosensitizers can rapidly induce apoptosis by triggering certain apoptotic events at the level of mitochondria , such as induction of the permeability transition