The laboratory is located at Istituto di Ricerche Farmacologiche "Mario Negri"-IRCCS, Via Mario Negri n.2, 20156 Milan, Italy.

 

Team members:

Prof. T. Borsello - Team Leader

Dr. G. Tommaselli

Dr. L. Colnaghi

Clara Alice Musi

Arianna Giani

Giacomo Marchini

 

 

The focus of the laboratory is to understand the molecular, cellular and neuronal network mechanisms that cause the deficits underlying acute and chronic diseases of the Central Nervous System. The laboratory is also dedicated to the research of new therapeutic targets for the development of new molecules for the treatment of neurodegeneration common to all brain diseases.

 

Scientific Queries:

1- Can specific inhibition of key proteins in the neurodegenerative process represent a new therapeutic strategy to counteract neurological disorders?

2- What are the cellular and intracellular signals that regulate the functional and/or pathological state of the synapse?

3- What are the regulatory mechanisms and thus potential therapeutic targets underlying synaptic dysfunction?

4- Which protein alterations related to neurodegeneration can be observed in peripheral tissues in early stages of the disease?

 

Primary goals:

1- Discover key proteins of neurodegeneration and their specific protein-protein interactions

2- Prevent their action through the design of specific cargo-bioactives to prevent the neurodegenerative process

3- Counteract the processes of neuronal dysfunction/death by enhancing neuroprotective mechanisms.

4- The stressed synapse: the new pathological focus to block neurodegeneration

5- Identify possible biomarkers for the early diagnosis of neurodegenerative diseases such as Alzheimer's disease

 

 

Methodologies and collaborations

In vitro

Hippocampal neuronal cultures

Hippocampal astrocytic cultures

Microglia extraction and purification

2D and 3D co-cultures of neurons/astrocytes/microglia

Organotypic cultures of hippocampus and cerebellum

Basic biochemistry and molecular biology techniques

TAT-HIV technology to introduce peptides into live cells

Dendritic spine detection, quantification and 3D reconstruction

In-life time-lapse microscopy

Electron microscopy and morphometric analysis of dendritic spines

LDH/MTT assay

Protein-protein interaction study

Superresolution microscopy

Fingerprint MassSpectromerty

 

In vivo

Expertise in microsurgery in rodents

Diverse drug delivery techniques and treatments in the chronic setting

Routine histological and biochemical techniques

Morphometric analysis (Neurolucida and Neuroexplorer)

Electron microscopy and immunocytochemical techniques pre- and post-inclusion

Behavioral tests able to analyze cognitive, mnemonic and locomotor disorders in rodents (6 Arms Water Maze, OF, NORT, Rotarod)

 

Collaborators

Prof. M. DiLuca, Unimi-Italia

Prof. F. Gardoni, Unimi- Italia

Prof. R. Melcangi, Unimi-Italia

Prof. M. Riva, Unimi-Italia

Prof. D. Caruso, Unimi-Italia

Prof. F. Tagliavini, Carlo Besta-Italia

Dr. G. Di Fede, Carlo Besta-Italia

Prof. P. Calabrese, Unipe-Italia

Prof. A. Renieri, Unisi-Italia

Prof. A. Vercelli, Unito-Italia

Dr. G. Forloni, IRCCS-Mario Negri-Italia

Dr. Pietro Veglianese, IRCCS-Mario Negri-Italia

Prof. E. Biasini, Unitn-Italia

Prof. Manuela Teresa Raimondi, Polimi-Italia

Prof. J. Mariani, Parigi, Francia

Dr. C. Bonny, Enterome Parigi, Francia

Prof. M. Repici, Birmingham, Regno Unito

Dr. M. Courtney, Turku, Finlandia

Dr. T. Meyer, AurisMedical Svizzera

Prof. I. Rainero, Unito-Italia

Dr. G. Zerbini, IRCCS-Ospedale San Raffaele

Dr. C. Sala, CNR, Milano

Dr. M. Sacchi, Ospedale San Giuseppe Milano

Prof. P. Nucci, Ospedale San Giuseppe Milano

Prof. R. Simo Canonge, Vall d’Hebron Research Institute, Spagna

 

Publications selection

Buccarello L, Sclip A, Sacchi M, Castaldo AM, Bertani I, ReCecconi A, Maestroni S, Zerbini G, Nucci P, Borsello T. The c-jun N-terminal kinase plays a key role in ocular degenerative changes in a mouse model of Alzheimer disease suggesting a correlation between ocular and brain pathologies. Oncotarget. 2017 Aug 3;8(47):83038-83051. doi: 10.18632/oncotarget.19886. eCollection 2017 Oct 10. PubMed PMID: 29137322; PubMed Central PMCID: PMC5669948.

Cimini S, Sclip A, Mancini S, Colombo L, Messa M, Cagnotto A, Di Fede G, Tagliavini F, Salmona M, Borsello T. The cell-permeable Aβ1-6A2VTAT(D) peptide reverts synaptopathy induced by Aβ1-42wt. Neurobiol Dis. 2016 May;89:101-11. doi: 10.1016/j.nbd.2015.12.013. Epub 2015 Dec 22. PubMed PMID: 26721320.

Sclip A, Tozzi A, Abaza A, Cardinetti D, Colombo I, Calabresi P, Salmona M, Welker E, Borsello T. c-Jun N-terminal kinase has a key role in Alzheimer disease synaptic dysfunction in vivo. Cell Death Dis. 2014 Jan 23;5:e1019. doi: 10.1038/cddis.2013.559. PubMed PMID: 24457963; PubMed Central PMCID: PMC4040696.

Vercelli A, Biggi S, Sclip A, Repetto IE, Cimini S, Falleroni F, Tomasi S, Monti R, Tonna N, Morelli F, Grande V, Stravalaci M, Biasini E, Marin O, Bianco F, di Marino D, Borsello T. Exploring the role of MKK7 in excitotoxicity and cerebral ischemia: a novel pharmacological strategy against brain injury. Cell Death Dis. 2015 Aug 13;6:e1854. doi: 10.1038/cddis.2015.226. PubMed PMID: 26270349; PubMed Central PMCID: PMC4558515.

Borsello T, Clarke PG, Hirt L, Vercelli A, Repici M, Schorderet DF, Bogousslavsky J, Bonny C. A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia. Nat Med. 2003 Sep;9(9):1180-6. Epub 2003 Aug 24. PubMed PMID: 12937412.