Research group: Marco Peviani

Even though neurons are the primary target of neurodegenerative diseases, neuroinflammatory processes contribute to shaping the neuronal microenvironment and have a direct impact on the disease progression. Reactive glial cells are involved in spreading of the pathology to other CNS districts and in progression of the disease towards late stages.
Our working hypothesis is that the heterogenous glial cell responses occurring during disease progression in ALS, as well as in other disorders, reflect not only the extent of neuronal demise in different regions, but also variable engagement in the attempts to cope with the neuronal damage. In this project, we shall exploit modern techniques for single-cell profiling in rodent models and human samples and novel cell-targeted nanovector platforms to obtain better insights into the complexity of glial-cell responses in health and disease.
We shall leverage this knowledge to achieve multiple drug/gene delivery and targeted engagement of specific reactive glial cell subtypes as a strategy to reshape neuro-supportive neuroinflammation and possibly slow down disease progression. In parallel, we plan to explore and validate novel disease-specific biomarkers that could be used to predict disease progression, determine eligibility for treatment, and/or assess target engagement, serving as valuable tools to aid in the translatability to the clinical setting.

Selected Publications:

• Heterogeneity of Neuroinflammatory Responses in Amyotrophic Lateral Sclerosis: A Challenge or an Opportunity? Cipollina G, Davari Serej A, Di Nolfi G, Gazzano A, Marsala A, Spatafora MG, Peviani M. Int J Mol Sci. 2020 Oct 25;21(21):7923. doi: 10.3390/ijms21217923.
• Synthesis and Characterization of a “Clickable” PBR28 TSPO-Selective Ligand Derivative Suitable for the Functionalization of Biodegradable Polymer Nanoparticles. Auriemma R, Sponchioni M, Capasso Palmiero U, Rossino G, Rossetti A, Marsala A, Collina S, Sacchetti A, Moscatelli D, Peviani M. Nanomaterials (Basel). 2021 Jun 28;11(7):1693. doi: 10.3390/nano11071693.
• Bitopic Sigma 1 Receptor Modulators to Shed Light on Molecular Mechanisms Underpinning Ligand Binding and Receptor Oligomerization. Rossino G, Rui M, Linciano P, Rossi D, Boiocchi M, Peviani M, Poggio E, Curti D, Schepmann D, Wünsch B, González-Avendaño M, Vergara-Jaque A, Caballero J, Collina S. J Med Chem. 2021 Oct 28;64(20):14997-15016. doi: 10.1021/acs.jmedchem.1c00886. Epub 2021 Oct 8.