The main interest of the “Inflammation and Neurodegeneration Laboratory” is to understand the contribution of immunity and inflammation to the development of neurodegenerative diseases, such as Parkinson’s disease, and to investigate the pathophysiological role of heme and iron in the brain.
The activation of the innate and adaptive immune response is a self-defensive reaction triggered to restore homeostasis and to eliminate harmful stimuli that compromise the integrity of the affected tissues. In the last decade, immunity and inflammation were shown to play an important role in a variety of neurological disorders, including Parkinson’s disease. This led to revise a long-held concept that the brain was an immune-privileged organ and to open a new field of investigation aimed to assess the contribution of immune cells to the pathogenesis of neurodegenerative diseases.
The main interest of our Laboratory is to assess the role of the immune response in the development of Parkinson’s disease and to investigate the molecular mechanisms underlying the involvement of heme and iron in neuroinflammation and neuronal death.
As an independent line of research, our Laboratory is also interested in assessing the pro-inflammatory role of heme in the pathogenesis of immune-mediated inflammatory diseases, such as spondyloarthritis, a rheumatic disease characterized by a progressive damage of the spine.
- Gozzelino R, Arosio P (2016) Iron Homeostasis in Health and Disease. Int J Mol Sci. 17(1). pii: E130. doi: 10.3390/ijms17010130.
- Arosio P, Carmona F, Gozzelino R, Maccarinelli F, Poli M. (2015) The importance of eukaryotic ferritins in iron handling and cytoprotection. Biochem J. 2015 Nov 15;472(1):1-15. doi: 10.1042/BJ20150787.
- “The importance of iron in pathophysiologic conditions” Frontiers Research Topic Ebook, Edited by: Raffaella Gozzelino and Paolo Arosio, Publisher: Frontiers Media SA, ISBN: 978-2-88919-524-4.
- Gozzelino R*. The pathophysiology of heme in the brain. Curr Alzheimer Research (In press).
- Yilmaz B, Portugal S, Tran TM, Gozzelino R, Ramos S, Gomes J, Regalado A, Cowan PJ, d’Apice AJF, Chong AS, Doumbo OK, Traore B, Crompton PD, Silveira H and Soares MP. Gut microbiota elicits a protective immune response against malaria transmission. Cell. 2014 Dec 4;159(6):1277-89.
- Soares MP, Gozzelino R and Weis S. Tissue damage control in disease tolerance. Trends Immunol. 2014 Aug 30.
- Figueiredo N, Chora A, Raquel H, Pejanovic N, Pereira P, Hartleben B, Neves-Costa A, Moita C, Pedroso D, Pinto A, Marques S, Faridi H, Costa P, Gozzelino R, Zhao JL, Soares MP, Gama-Carvalho M, Martinez J, Zhang Q, Döring G, Grompe M, Simas JP, Huber TB, Baltimore D, Gupta V, Green DR, Ferreira JA, Moita LF. Anthracyclines induce DNA damage response mediated protection against severe sepsis. Immunity. 2013 Nov 14;39(5):874-84.
- Gozzelino R, Andrade BB, Larsen R, Luz NF, Vanoaica L, Seixas E, Coutinho A, Cardoso S, Rebelo S, Poli M, Barral-Netto M, Darshan D, Kühn L, Soares MP. Metabolic adaptation to tissue iron overload confers tolerance to malaria. Cell Host Microbe. 2012 Nov 15;12(5):693-704.
- Larsen R, Gouveia Z, Soares MP, Gozzelino R. Heme Cytotoxicity And The Pathogenesis of Immune Mediated Inflammatory Diseases. Front Pharmacol. 2012;3:77.
- Larsen R, Gozzelino R, Jeney V, Tokaji L, Bonaparte D, Cavalcante M, Chora Â, Ferreira A, Marguti I, Cardoso S, Sepulveda N, Smith A, Soares MP. Targeting free heme to suppress the pathogenesis of severe sepsis. Sci Transl Med. 2010 Sep 29;2(51):51ra71.
- Gozzelino R, Jeney V, Soares MP. Mechanisms of cell protection by heme oxygenase-1. Annual Rev Pharmacol Toxicol. 2010;50:323-54. Review.
- Seixas E*, Gozzelino R*, Chora A, Ferreira A, Silva G, Larsen R, Rebelo S, Penido C, Smith NR, Coutinho A, Soares MP. Heme oxygenase-1 affords protection against noncerebral forms of severe malaria. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15837-42. (* equal contribution).
- Gozzelino R, Sole C, Llecha N, Segura MF, Moubarak RS, Iglesias-Guimarais V, Perez-Garcia MJ, Reix S, Zhang J, Badiola N, Sanchis D, Rodriguez-Alvarez J, Trullas R, Yuste VJ, Comella JX. Bcl-xL regulates TNF-alpha-mediated cell death independently of NF-kB, FLIP and IAPs. Cell Res. 2008 Oct;18(10):1020-36.
- Segura MF, Sole C, Pascual M, Moubarak RS, Perez-Garcia MJ, Gozzelino R, Iglesias V, Badiola N, Bayascas JR, Llecha N, Rodriguez-Alvarez J, Soriano E, Yuste VJ, Comella JX. The long form of Fas apoptotic inhibitory molecule is expressed specifically in neurons and protects them against death receptor-triggered apoptosis. J Neurosci. 2007 Oct 17;27(42):11228-41.
- Sole C, Dolcet X, Segura MF, Gutierrez H, Diaz-Meco MT, Gozzelino R, Sanchis D, Bayascas JR, Gallego C, Moscat J, Davies AM, Comella JX. The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-kB signaling. J Cell Biol. 2004 Nov 8;167(3):479-92. Epub 2004 Nov 1.
• Jaime C. Branco, Rheumatological Diseases Unit, CEDOC/FCM, Lisbon, Portugal.
• Joaquim Ferreira, Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal.
• Miguel P. Soares, Inflammation Laboratory, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
• Luis Ferreira Moita, Innate Immunity and Inflammation Laboratory, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
• Emanuela Tolosano, Department of Molecular Biotechnologies and Health Sciences, Molecular Biotechnology Center (MBC), University of Turin, Italy.
• Paolo Arosio, Department of Pediatrics and Biomedical Technologies, University of Brescia, Italy.