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Laboratory of Neuronal death and Neuroprotection  

The lab is located in the IRCCS-Institute of Pharmacological Research "Mario Negri", Via la Masa 19, 20156 Milano, Italy.

lab prof Borsello

 

Research topics

The laboratory studies the intracellular pathways of apoptotic necrotic and autophagic neuronal death. We are interested in the regulation of signalling network underline astrocyte-neuron-microglia-synapse interactions in healthy and stress conditions.

Main Aims

1- To discover key modulator of neurodegenerative pathways and their cross-talks

2- To prevent key players in neurodegenerative pathways

3- To limit neuronal dysfunction/death and enhancing neuroprotective mechanisms 

Scientific questions

1-Can key player inhibitors represent a future therapeutic strategy against brain diseases?

2-What cues can trigger or maintain the neuroprotective or detrimental state of the synapse?

3-What are the targetable signaling underlying the synaptic dysfunction?

 

Techniques:

"In vitro"
Hippocampal neuronal cultures
Hippocampal astrocytes cultures
Microglia extraction and purification
Co-culture neurons/astrocytes/microglia
Organotypic culture of hippocampus and cerebellum
Basic biochemistry and Molecular Biology techniques
TAT-HIV technology to introduce peptides into living cells
Spine detection, quantification and 3D Reconstruction
Time-lapse in-life microscopy
Electron microscopy and morphometric analysis of dendritic spines
LDH/MTT Assay

"In vivo"
Expertise in microsurgery of rodents
Routine histological techniques
Neurolucida and Neuroexplorer morphometric-analysis
Electron microscopy/ pre- and post-embedding immunocytochemical techniques
Behavioural tests able to identify cognitive, mnemonic and locomotor impairments (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. A. Maggi, Unimi-Italia
  • Prof. F. Tagliavini, Carlo Besta-Italia
  • Dr. G. Di Fede, Carlo Besta-Italia
  • Prof. P. Calabrese, Unipe-Italia
  • Prof. A. Reniaeri, Unisi-Italia
  • Prof. M. Miniaci, Unina-Italia
  • Prof. A. Vercelli, Unito-Italia
  • Prof. M. Giustetto, 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

 

Selected publications

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
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