Cellular and Molecular Neuropharmacology

Macroarea: Pharmacology

ERC sectors: LS1_10 Molecular mechanisms of signalling pathways;  LS3_5 Cell signalling and signal transduction; LS5_1 Neural cell function, communication and signalling, neurotransmission in neuronal and/or glial cells; LS5_7 Neurological disorders (e.g. neurodegenerative diseases, seizures); LS7_4 Pharmacology and pharmacogenomics (including drug discovery and design, drug delivery and therapy, toxicology)

Lab manager: Alessia Pascale (PO), Annalisa Barbieri (RU), Nicoletta Marchesi (RTDa)

Scientific Consultant: Stafano Govoni (Prof. Emerito)

Technician: Federica Boschi

1. “Characterization of the role of the ubiquitous ELAV/HuR protein in diabetic retinopathy and other eye diseases”. The project also aims at the search of new molecules that could interfere with this pathway. In collaboration with: C. Bucolo, F. Drago, R. Pignatello (Catania University) and F. Bandello, G. Zerbini (San Raffaele, Milan).

2. “Study on the biologic effects of ELAV-mimicking compounds or of molecules able to activate, via PKC, ELAV proteins in neurodegenerative diseases”. In collaboration with: S. Collina (Pavia University) and with a group of Finnish Pharmaceutical Chemists and Pharmacologists (Helsinki University).

3. “Involvement of oxidative stress and ELAV/HuR protein in Multiple Sclerosis”. The project also aims at investigating the effect of drugs used in Multiple Sclerosis current therapy on these pathways. In collaboration with: R. Bergamaschi, (IRCCS, Mondino), N. Galeotti (Firenze University), P. Giunchedi (Sassari University), C. Bonferoni (Pavia University).

4. “Role of ELAV/HuR protein in ischemic stroke and neuroprotective mechanisms”. In collaboration with: K. Pawletko and H. Jędrzejowska-Szypułka (University of Silesia, Katowice, Poland).

5. “Involvement of ELAV proteins in gut microbiota dysbiosis”. In collaboration with: C. Giaroni (Insubria University), M. Vairetti (Pavia University).

• SHORT- AND LONG-TERM EXPRESSION OF VEGF: A TEMPORAL REGULATION OF A KEY FACTOR IN DIABETIC RETINOPATHY. Bucolo C., Barbieri A., Viganò I., Marchesi N., Bandello F., Drago F., Govoni S., Zerbini G., Pascale A. Frontiers in Pharmacology - Section "Experimental Pharmacology and Drug Discovery". 12:707909, 2021. https://doi.org/10.3389/fphar.2021.707909
• TARGETING THE MICROBIOTA IN PHARMACOLOGY OF PSYCHIATRIC DISORDERS. Pascale A., Marchesi N., Govoni S., Barbieri A. Pharmacol. Research 157:104856, 2020. https://doi.org/10.1016/j.phrs.2020.104856
• UNRAVELING A NEW PLAYER IN MULTIPLE SCLEROSIS PATHOGENESIS: THE RNA-BINDING PROTEIN HUR. Pistono C., Monti M.C., Marchesi N., Boiocchi C., Campagnoli L.I.M., Morlotti D., Cuccia M., Govoni S., Montomoli C., Mallucci G., Bergamaschi R., Pascale A. Multiple Sclerosis and Related Disorders 41:102048, 2020. https://doi.org/10.1016/j.msard.2020.102048
• TARGETING VEGF IN EYE NEOVASCULARIZATION: WHAT’S NEW? A COMPREHENSIVE REVIEW ON CURRENT THERAPIES AND OLIGONUCLEOTIDE-BASED INTERVENTIONS UNDER DEVELOPMENT. Amadio M., Govoni S., Pascale A. Pharmacol. Research. 103:253-69, 2016.  https://doi.org/10.1016/j.phrs.2015.11.027
• THE C1 DOMAIN-TARGETED ISOPHTHALATE DERIVATIVE HMI-1B11 PROMOTES NEURITE OUTGROWTH AND GAP-43 EXPRESSION THROUGH PKCa ACTIVATION IN SH-SY5Y CELLS. Talman V., Amadio M., Osera C., Sorvari S., Boije af Gennäs G., Yli-Kauhaluoma J., Rossi D., Govoni S., Collina S., Ekokoski E., Tuominen R.K. and Pascale A. Pharmacol. Research 73: 44-54, 2013. https://doi.org/10.1016/j.phrs.2013.04.008
• THE COMPLEX WORLD OF POST-TRANSCRIPTIONAL MECHANISMS: IS THEIR DEREGULATION A COMMON LINK FOR DISEASES? FOCUS ON ELAV-LIKE RNA-BINDING PROTEINS. Pascale A. and Govoni S. Cell. Mol. Life Sci. 69(4): 501-517, 2012. doi:10.1007/s00018-011-0810-7 
• THE PKCβ/HUR/VEGF PATHWAY IN DIABETIC RETINOPATHY. Amadio M., Bucolo C., Leggio G.M., Drago F., Govoni S. and Pascale A. Biochem. Pharmacol. 80: 1230-1237, 2010. https://doi.org/10.1016/j.bcp.2010.06.033
• DISCOVERY OF SMALL PEPTIDES DERIVED FROM ELAV PROTEINS STRUCTURE SHOWING RNA-STABILIZING PROPERTIES. Rossi D., Amadio M., Carnevale Baraglia A., Azzolina O., Ratti A., Govoni S., Pascale A. and Collina S. J. Med. Chem. 52: 5017-5019, 2009. doi:10.1021/jm900741e 
• NEURONAL ELAV PROTEINS ENHANCE mRNA STABILITY BY A PKCα-DEPENDENT PATHWAY. Pascale A., Amadio M., Scapagnini G., Lanni C., Racchi M., Provenzani A., Govoni S., Alkon D.L. and Quattrone A. Proc. Natl. Acad. Sci. USA. 102(34): 12065-12070, 2005. https://doi.org/10.1073/pnas.0504702102
• INCREASE OF THE RNA-BINDING PROTEIN HUD AND POST-TRANSCRIPTIONAL UP-REGULATION OF THE GAP-43 GENE DURING SPATIAL MEMORY. Pascale A., Gusev P.A., Amadio M., Dottorini T., Govoni S., Alkon D.L. and Quattrone A. Proc. Natl. Acad. Sci. USA. 101(5): 1217-1222, 2004. https://doi.org/10.1073/pnas.0307674100

National collaborations

• Università di Catania
• IRCCS, C. Mondino, Pavia
• Università degli Studi di Firenze
• IRCCS Ospedale San Raffaele, Università Vita-Salute, Milano
• Università dell’Insubria
• Università di Sassari

International collaborations

• Università della Silesia, Katowice, Polonia; Università di Helsinki, Finlandia

• New pharmacological targets to cure disabling retinal diseases
• PRIN 2020 Involvement of ELAV/HuR protein in Multiple sclerosis

The lab experience is focused on molecular pharmacology and neuropharmacology fields. The research is especially addressed to signal transduction mechanisms, with a focus on the RNA-stabilizing proteins ELAV in different physiologic and pathologic contexts, such as memory and cognitive alterations associated to aging and Alzheimer’s disease, diabetic retinopathy, oxidative stress, autophagy, and more recently in dysbiosis. Useful instrumentation: bench-top ultracentrifuge