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Anna Caretto

Contatti

Tutore

Prof.ssa Marina Maria Boido
Prof. Alessandro Vercelli

Tesi di dottorato

Mitochondria are dynamic organelles that play a key role in several metabolic pathways, which help to maintain cellular homeostasis. Their involvement in the pathogenesis of several neurodegenerative diseases (e.g. Parkinson’s, Alzheimer’s and Huntington’s diseases and Amyotrophic Lateral Sclerosis) has become increasingly more evident: indeed, these pathologies seem to share both a morphological and a functional “mitochondrial switch” that occurs in response to a condition of stress. Recently similar alterations have been observed also in Spinal Muscular Atrophy (SMA), a motor neuron (MN) pediatric disease caused by a low expression of survival motor neuron (SMN) protein. SMA MNs are characterized by several mitochondrial abnormalities, including fragmentation, impaired membrane potential and altered mobility. Since MNs require a high energy rate, such mitochondrial alterations could explain their susceptibility to the disease. Moreover it has been observed that not only MNs but also other peripheral tissues requiring high energetic levels (as skeletal muscles and myocardium) are affected by SMA.

The current available therapies (SMN-dependent) unfortunately show several limitations, such as high costs, still unknown long-term effects and some side effects; moreover, they disregard SMN-independent targets and their efficacy is strictly linked to the onset of the treatment (late-treated patients show a lower rescue). Therefore, the search for new therapeutic strategies for SMA is necessary and mitochondria are becoming a new field of investigation for the identification of novel targets aiming at the maintenance of their integrity.

The aim of this project is to identify new molecules for SMA therapy, exploiting a “drug repositioning” strategy: this approach consists in the identification of drugs usually administered for the treatment of specific pathologies that can be tested for different indications, reducing time and costs for their clinical application.

To this aim, we will exploit a computational approach in order to identify SMN-anticorrelated genes that are involved in mitochondrial processes. The expression of two genes is anticorrelated when they show complementary expression profiles across many experiments. We aim to identify genes strongly anticorrelated with SMN, involved in mitochondrial function. As a first validation of the procedure, we will assess whether the expression of these genes is modified by SMN deficiency in CNS and some peripheral tissues (skeletal muscles and heart) obtained from SMAdelta7 mice (an intermediate model of SMA). We will test whether the modulation of these genes may regulate mitochondrial dynamics in vitro in neuronal cells (primary cortical neurons obtained from SMAdelta7 and a MN cell line). Finally we plan to perform some in vivo analysis, to assess the behavioral, histological and molecular outcomes obtained by genetically or pharmacologically modulating the function of the strongest targets identified in vitro.

This strategy will help us in better understanding the effects of SMN deletion on metabolic pathways and could lead to the identification of approved compounds that could revert altered mitochondrial dynamics in SMA.

Attività di ricerca

2022

  • Caretto A.; Di Cunto F.; Boido M.; Vercelli A. Drug repositioning as a therapeutic strategy to target mitochondria in Spinal Muscular Atrophy. ENCODS2022. July 7th-8th, Paris.
  • Caretto A.; Di Cunto F.; Boido M.; Vercelli A. Investigation of mitochondrial SMN1-anticorrelated genes as possible therapeutic targets for Spinal Muscular Atrophy. National meeting of PhD Students in Neuroscience. June 11th, Brescia.
  • Caretto A.; Di Cunto F.; Boido M.; Vercelli A. Targeting of altered mitochondrial genes as a therapeutic strategy for Spinal Muscular Atrophy. 94° Congresso Nazionale SIBS. April 6th-9th, Turin.

2021

  • Caretto A.; Gesmundo I.; Schellino R.; Schally A.V.; Granata R.; Boido M. and Vercelli A. Investigating a new therapeutic role of the GHRH agonist MR409 in an experimental model of Spinal Muscular Atrophy. Fourth brainstorming research assembly for young neuroscientists (BraYn 2021). October 21st-23rd, Pisa.
  • Boido M., Gesmundo I., Caretto A., Schellino R., Schally A.V., Granata R., Valsecchi V., Hettwer S., Vercelli A. Spinal Muscular Atrophy, more than a motor neuron disease: the contribution of neuromuscular junction dysfunctions to disease progression. XIX Congresso Nazionale SINS. September 9th-11th, 2021, Virtual congress.
  • Boido M.; Gesmundo I.; Caretto A.; Schellino R.; Schally A.V.; Granata R.; Vercelli A. A new potential supportive role of MR409, a GHRH agonist, in an experimental mouse model of Spinal Muscular Atrophy. 2021 Virtual SMA Research & Clinical Care Meeting. June 9th-11th, 2021.

2020

  • Caretto A.; Gesmundo I.; Schellino R.; Schally A.V.; Boido M.; Granata R. and Vercelli A. Efficacy evaluation of the GHRH agonist MR409 in a SMA murine model. 30th National Conference of the Italian Group for the Study of Neuromorphology (GISN). European Journal of Histochemistry. ISSN 1121-760X volume 64/ supplement 3, 2020.
  • Caretto A.; Gesmundo I.; Schellino R.; Schally A.V.; Boido M.; Granata R. and Vercelli A. A new potential supportive role of MR409, a GHRH agonist, in an experimental mouse model of Spinal Muscular Atrophy. Motor Neuron Diseases understanding the pathogenetic mechanisms to develop therapies. November 6th-7th, 2020, virtual conference.
  • Stanga S.; Caretto A.; Boido M.; Kienlen-Campard P.; Vercelli A. Mitochondrial dysfunctions are early events eliciting the shift towards pathological neurobiological processes. Morfologia e dintorni (3° incontro nazionale). September 26th, 2020, virtual conference.

2022

  • Poster at ENCODS2022. July 7th-8th, Paris.
  • Poster at National meeting of PhD Students in Neuroscience. June 11th, Brescia.
  • Poster at 94° Congresso Nazionale SIBS. April 6th-9th, Institute of Anatomy, Corso Massimo D'Azeglio 52, Turin.

2021

  • Oral comunication at "Fourth brainstorming research assembly for young neuroscientists". BraYn 2021. October 21st-23rd, 2021, Pisa.

2020

  • Short talk comunication at "30th National Conference of the Italian Group for the Study of Neuromorphology". GISN 2020. November 12th-14th, 2020, virtual conference.
  • Poster at "Motor Neuron Diseases understanding the pathogenetic mechanisms to develop therapies". November 6th-7th, 2020, virtual conference.
  • Poster at "Morfologia e dintorni (2° incontro nazionale)". February, 22nd-23rd, 2020, Institute of Anatomy, Corso Massimo D'Azeglio 52, Turin.

2022

  • "How we reason" - M.Bucciarelli - Toolbox Course, May 18th and 25th. 

2021

  • "In vitro and ex vivo approaches to study neural cells: from primary cultures to human organoids" - A. Buffo, E. Boda, G. Pallavicini, S. Gribaudo, V. Cerrato. - Toolbox Course, June 11th, 14th, 21st, 28th.
  • "Ethics of research and Responsible research: an introduction" - D. Ovadia - Toolbox Course, May 3rd, 10th, 17th, 24th.
  • "Glycogen synthase kinase-3 (GSK-3): a potential biomarker in mood disorders" - G.Maina, F. Tempia, E. Hoxha, G. Rosso. - Advanced Course, May 20th 2021.
  • "From neural cell excitability to brain circuit recording, visualization and manipulation" - F. Ferrini, B. Sacchetti, S. Bovetti, E. Hoxha. - Toolbox Course, February 1st - 4th - 8th - 11th 2021.
  • "Basic Concepts of Statistics" - A. Ricotti - Toolbox Course, January 25th - 26th 2021.

2020

  • PhD Journal Club 2020/2021.
  • "Introduction to Research methodology" - D. Romano - Toolbox Course, December 4th - 11th - 18th 2020.
  • "Clinical, methodological and theoretical aspects of translational and cognitive neuroscience" - A. Berti, A. Chiò, M. Giustetto - Toolbox Course, November 27th 2020.
  • "Inaugurazione anno dottorale 2020-2021" - S.Geuna, A.Rizzuti - Meeting, November 5th 2020.
  • "Welcome Meeting for PhD Students XXXVI cycle" - M.Sassoè - Meeting, 21th October 2020.

2022

  • "NICO NeuroWebinar", virtual conferences.

2021

  • BraYn. Third brainstorming research assembly for young neuroscientists. 25th-26th November 2020, web conference.
  • "NICO NeuroWebinar", virtual conferences.

Stanga, S.; Caretto, A.; Boido, M.; Vercelli, A. Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases. Int. J. Mol. Sci. 2020, 21, 3719.

2021

  • Caretto A.; Gesmundo I.; Schellino R.; Schally A.V.; Granata R.; Boido M. and Vercelli A. Investigating a new therapeutic role of the GHRH agonist MR409 in an experimental model of Spinal Muscular Atrophy. Neurol. Int. 202214(1), 109-157; https://doi.org/10.3390/neurolint14010010

2020

  • Caretto A.; Gesmundo I.; Schellino R.; Schally A.V.; Boido M.; Granata R. and Vercelli A. Efficacy evaluation of the GHRH agonist MR409 in a SMA murine model. 30th National Conference of the Italian Group for the Study of Neuromorphology (GISN). European Journal of Histochemistry. ISSN 1121-760X volume 64/ supplement 3, 2020.
Ultimo aggiornamento: 09/07/2022 19:10
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