Biologia e Farmacologia delle malattie oculari legate all’invecchiamento

Macroarea: Farmacologia

Settori ERC: LS1 Molecules of Life: Biological Mechanisms, Structures and Functions, LS3 Cellular, Developmental and Regenerative Biology, LS4 Physiology in Health, Disease and Ageing, LS5 Neuroscience and Disorders of the Nervous System, LS7 Prevention, Diagnosis and Treatment of Human Diseases

Referente: Marialaura Amadio (PA)

Consulente Scientifico: Stefano Govoni (Prof. Emerito)

Il contesto è la biologia dell’invecchiamento e le patologie della retina. L’interesse principale è per la farmacologia cellulare e molecolare, in particolare per il fattore di trascrizione Nrf2 e la famiglia delle proteine ELAV (entrambi regolatori dell’espressione genica, l’una a livello trascrizionale, l’altra post-trascrizionale attraverso la regolazione del metabolismo degli RNA). Lo studio ha l’obiettivo di comprendere il ruolo di tali proteine in contesti fisio-patologici. La ricerca include la modulazione farmacologica di Nrf2 e ELAV come possibili bersagli terapeutici di interesse per le malattie dell’occhio legate all’invecchiamento.

• Amadio M, Bucolo C, Leggio GM, Drago F, Govoni S, Pascale A. The PKCbeta/HuR/VEGF pathway in diabetic retinopathy. Biochem Pharmacol. 2010; 80(8):1230-7. https://doi.org/10.1016/j.bcp.2010.06.033
• Viiri J, Amadio M, Marchesi N, Hyttinen JM, Kivinen N, Sironen R, Rilla K, Akhtar S, Provenzani A, D’Agostino VG, Govoni S, Pascale A, Agostini H, Petrovski G, Salminen A, Kaarniranta K. Autophagy Activation Clears ELAVL1/HuR-Mediated Accumulation of SQSTM1/p62 during Proteasomal Inhibition in Human Retinal Pigment Epithelial Cells. PLoS One 2013;8(7):e69563. https://doi.org/10.1371/journal.pone.0069563
• Amadio M, Govoni S, Pascale A. Targeting VEGF in eye neovascularization: What's new?: A comprehensive review on current therapies and oligonucleotide-based interventions under development. Pharmacol Res. 2016;103:253-69. https://doi.org/10.1016/j.phrs.2015.11.027
• Marchesi N, Amadio M, Colombrita C, Govoni S, Ratti A, Pascale A. PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells. J Alzheimers Dis. 2016;54(2):535-47. doi: 10.3233/JAD-160299.
• Amadio M, Pascale A, Cupri S, Pignatello R, Osera C, D'Agata V, D'Amico AG, Leggio GM, Ruozi B, Govoni S, Drago F, Bucolo C. Nanosystems based on siRNA silencing HuR expression counteract diabetic retinopathy in rat. Pharmacol Res. 2016;111:713-20. https://doi.org/10.1016/j.phrs.2016.07.042
• Smedowski A, Liu X, Podracka L, Akhtar S, Trzeciecka A, Pietrucha-Dutczak M, Lewin-Kowalik J, Urtti A, Ruponen M, Kaarniranta K, Varjosalo M, Amadio M. Increased intraocular pressure alters the cellular distribution of HuR protein in retinal ganglion cells - A possible sign of endogenous neuroprotection failure. Biochim Biophys Acta. 2018;1864(1):296-306. https://doi.org/10.1016/j.bbadis.2017.10.030
• Marchesi N, Thongon N, Pascale A, Provenzani A, Koskela A, Korhonen E, Smedowski A, Govoni S, Kauppinen A, Kaarniranta K, Amadio M. Autophagy Stimulus Promotes Early HuR Protein Activation and p62/SQSTM1 Protein Synthesis in ARPE-19 Cells by Triggering Erk1/2, p38MAPK, and JNK Kinase Pathways. Oxid Med Cell Longev. 2018:4956080. https://doi.org/10.1155/2018/4956080
• Pietrucha-Dutczak M, Amadio M, Govoni S, Lewin-Kowalik J, Smedowski A. The Role of Endogenous Neuroprotective Mechanisms in the Prevention of Retinal Ganglion Cells Degeneration. Front Neurosci. 2018 Nov 15;12:834. https://doi.org/10.33
• Felszeghy S, Viiri J, Paterno JJ, Hyttinen JMT, Koskela A, Chen M, Leinonen H, Tanila H, Kivinen N, Koistinen A, Toropainen E, Amadio M, Smedowski A, Reinisalo M, Winiarczyk M, Mackiewicz J, Mutikainen M, Ruotsalainen AK, Kettunen M, Jokivarsi K, Sinha D, Kinnunen K, Petrovski G, Blasiak J, Bjørkøy G, Koskelainen A, Skottman H, Urtti A, Salminen A, Kannan R, Ferrington DA, Xu H, Levonen AL, Tavi P, Kauppinen A, Kaarniranta K. Loss of NRF-2 and PGC-1α genes leads to retinal pigment epithelium damage resembling dry age-related macular degeneration. Redox Biol. 2019 Jan;20:1-12. https://doi.org/10.1016/j.redox.2018.09.011
• Catanzaro M, Lanni C, Basagni F, Rosini M, Govoni S, Amadio M. Eye-Light on Age-Related Macular Degeneration: Targeting Nrf2-Pathway as a Novel Therapeutic Strategy for Retinal Pigment Epithelium. Front Pharmacol. 2020 Jun 5;11:844. https://doi.org/10.3389/fphar.2020.00844

Collaborazioni Nazionali

• University of Bologna, Dept. of Pharmacy and Biotechnologies, Italy
• University of Pisa, Dept. of Biology, Italy
• Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia

Collaborazioni Internazionali

• Medical University of Silesia, School of Medicine, Dept. of Ophthalmology, Katowice, Poland
• University of Eastern Finland, Dept. of Ophthalmology, Kuopio, Finland.

Saggi biologici cellulari e molecolari, saggi farmacologici – test in vitro