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Biology & Pharmacology of Age-related Ocular Pathologies

Macroarea: Pharmacology

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

Team dell'Unità di Ricerca

Lab Manager: Marialaura Amadio (PA)

Scientific Consultant: Stefano Govoni (Prof. Emerito)

Research Lines

The context is the biology of aging and retinal diseases. The interest is for cellular and molecular pharmacology, especially for the Nrf2 factor and the RNA-binding ELAV proteins (both gene expression regulators, acting at transcriptional and post-transcriptional level, respectively). The aim is to understand the roles of these proteins in physio-pathological contexts. The research includes the pharmacological modulation of Nrf2 and ELAV as potential therapeutic targets in age-related ocular pathologies.

Pubblication
  • 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
Collaboration

National Collaboration

  • 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

International Collaboration

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

Cellular, molecular biology and pharmacological assays - in vitro, cell culture