Group leader: Alessandro Vercelli
Iron arm with dementia: iron and mitochondria as new targets against Alzheimer's disease
2022-2024 | Fondazione Cassa di Risparmio di Torino (CRT)
Because of the increase ageing of the population, neurodegenerative diseases are dramatically incrementing; indeed, ageing is the main risk factor for dementia. The project aims to: i) unreveal new neurobiological mechanisms underpinning neurodegenreation, ii) identify new biomarkers able to predict cognitive decline and iii) new targtes for the development of drugs for Alzheimer's disease cure. We will study the mechanisms related to iron metabolism in the brain and specifically in the cerebral cortex and in the hippocampus, areas deeply touched by neurodegenerative processes.
The role of SMN protein in translation: implications for Spinal Muscular Atrophy
2019-2022 | Fondazione Telethon
Marina Boido, head of research unit
Research network: coordinator Gabriella Viero, CNR, Trento
The aim of the project is to understand how alterations of SMN expression can affect translation (i.e. protein synthesis) in case of SMA. The study will be important not only to better understand the role of SMN (whose functions are only partially known) and the pathogenesis of the disease, but also to design innovative effective therapies to counteract this pathology.
Development of combinatorial therapies for SMA
2019-2020 | AFM Telethon
Marina Boido, head of research unit
Research network: coordinator Ruben Artero, University of Valencia, Spagna; Cécile Martinat, I-STEM, Corbeil-Essonnes, France
In this project we will select and test in vitro and in vivo some FDA-approved drugs (alone or in combination), to provide the most efficient “cocktail” of therapeutics able to systemically increase SMN protein levels. Indeed we aim for discovery of an orally administered drug which will not only increase the SMN protein levels in motoneurons, but also in other affected tissues.
Mitochondria in Spinal Muscular Atrophy: dysfunctions and mitophagy
2018-2020 | Fondazione CRT - Richieste Ordinarie 2017
The aim of the project is to deeply study mitochondria dysfunction and mitophagy in SMA. We intend to understand how the pathogenesis of SMA is linked to mitochondria alterations. The in-depth analysis of these aspects will contribute both to shed light on the complex mechanisms that cause SMA, but also to identify new therapeutic targets.
Identification of new druggable targets and potential therapeutic compounds for Spinal Muscular Atrophy, using a C.elegans model of neurodegeneration
2017-2020 | Fondazione Telethon
Alessandro Vercelli, head of research unit
Research network: coordinator Elia Di Schiavi, CNR, Napoli
The project will help us to identify new genetic partners interacting with SMN and to understand how they influence smn-1 dependent phenotypes; we also intend to identify new molecules able to prevent neurodegeneration caused by the lack of SMN.
My-AHA - My Active and Healthy Ageing
January 2016-2019 | Horizon 2020
Coordinator Alessandro Vercelli, NICO - University of Torino
The consortium is made of: Istituto Mario Boella (Torino), the Universities of Siegen and Koln (D), Loughborough (GB), Instituto de Biomecanica Valencia (E), Fraunhofer Portugal, Johanniter Austerreich (A), Kasa Solution (D), VitalinQ (N), GESMED (E). To the consortium participate as Extra-EU partners Seul National University (South Korea), Tohoku University (Japan), University of the Sunshine Coast (Australia), and the JIN company (Japan).
Aims and Relevance
The main aim of my-AHA is to reduce frailty risk by improving physical activity and cognitive function, psychological state, social resources, nutrition, sleep and overall well-being. It will empower older citizens to better manage their own health, resulting in healthcare cost savings. my-AHA will use state-of-the-art analytical concepts to provide new ways of health monitoring and disease prevention through individualized profiling and personalized recommendations, feedback and support.
An ICT-based platform will detect defined risks in the frailty domains early and accurately via non-stigmatising embedded sensors and data readily available in the daily living environment of older adults. When risk is detected, my-AHA will provide targeted ICT-based interventions with a scientific evidence base of efficacy, including vetted offerings from established providers of medical and AHA support. These interventions will follow an integrated approach to motivate users to participate in exercise, cognitively stimulating games and social networking to achieve long-term behavioural change, sustained by continued end user engagement with my-AHA.
more information > www.activeageing.unito.it
Neurostemcellrepair - European stem cell consortium for neural cell replacement, reprogramming and functional brain repair
2013-2017 | FP7 European Union
E Fucà, A Buffo, D Carulli participating in the research unit headed by A Vercelli
Research network: Elena Cattaneo, University of Milan, coordinator, Ernest Arenas, Karoliska Institute, deputy coordinator, Parmar Malin, University of Lund, Stephen Dunnet, University of Cardiff, Oliver Brustle, University of Bonn, Roger Barker, University of Cambridge, Charles ffrench-Constant, University of Edimburgh, Andreas Bosio, Milteny, Ida Biunno, Isenet).
This project aims at developing new strategies for stem cell therapies in Hungtington and Parkinson diseases, including acquisition of specific neuronal identities and functional integration in the recipient brain. We contribute our expertise in rodent models of Hungtington disease, and analyse how specific training activities can ameliorate differentiation and integration of grafted cells.
more information > www.neurostemcellrepair.org
Motor neuron death in Spinal Muscular Atrophy (SMA): new animal models and innovative therapeutic strategies
2011-2015 | Italian Ministry of Health RF-2009-1475235
The proposed research project will aggregate: i) the Molecular Neuroanatomy and Pathogenesis Unit (G. Battaglia), at the IRCCS Foundation Neurological Institute "C. Besta" in Milano; ii) the Molecular and Computational Biology lab (F. Di Cunto) at the Molecular Biotechnology Center in Torino; iii) the C.elegans Neurobiology lab (E. Di Schiavi) at the Institute of Genetics and Biophysics of the CNR in Napoli; and iv) the lab of Developmental Neuroanatomy (A. Vercelli) at the NICO.
Spinal Muscular Atrophy or SMA is a severe autosomal recessive disease characterized by selective motor neuron degeneration. SMA is the leading genetic cause of infant mortality, with an incidence of 1:10.000 live births and an estimated carrier frequency of 1:35. The SMA determining gene was discovered in 1995 and termed survival motor neuron (SMN) gene.
The main protein product of the SMN1 gene, the FL-SMN protein, has its primary and most important role in spliceosomal assembly and pre-mRNAs maturation. However, how reduced FL-SMN levels lead to selective degeneration of motor neurons in SMA still remains elusive. Accordingly, no effective therapy is up to now available for affected children.
A novel, truncated isoform of the FL-SMN protein, a-SMN or axonal SMN, with selective expression in the axons of spinal cord motor neurons, has been recently reported by our group. We intend to verify the in vivo function and therapeutic properties of the FL-SMN and a-SMN proteins in both invertebrate and mammalian experimental settings.
Generation of authentic human striatal neurons from pluripotent stem cells for transplantation in Huntington's disease
2013-January 2016 | PRIN - Italian Ministry of University and Research
Coordinator: Elena Cattaneo; Head of local research unit: Alessandro Vercelli
Research Network: Biella Gerardo Rosario, University of Pavia; Biunno Ida, Cnr; Moresco Rosa Maria, University Milano-Bicocca
The anatomy of the striatum in mammals is characterized by medium-sized spiny GABAergic projection neurons and by 5% interneurons. On immunohistochemical and histochemical grounds, the striatum can be subdivided in lightly labeled striosomes and an intensely labeled matrix, in which neurons are differentially organized. The striatum is part of neural circuits which play a role in motor behavior and in the mechanisms of reward. The anatomical organization is completely disrupted in Huntington's disease, where projection neurons degenerate massively, causing a secondary neuronal death in the substantia nigra, to which the striatum is strongly interconnected.
The aim of the consortium is to explore the potential for a specific set of stem cells, human ventral striatal progenitors, derived from embryonic stem cells, to replace lost projection neurons in a rat experimental model of Huntington's disease.
In the frame of this project, UNITO will be responsible for studying the anatomical integration of stem cells in the striatum. The results obtained by our UNIT will be compared with those obtained in the same animals on motor behavior in order to correlate improvement in motor performance with the proper differentiation of stem cells and their integration into neural circuits.
Use of biomimetic scaffolds and stem cells to support the regeneration of the injured spinal cord
2014-2016 | Fondazione CRT
Marina Boido, NICO co-PI with Gianluca Ciardelli e Chiara Tonda-Turo, Politecnico di Torino
The project derives from a collaboration between UNITO and POLITO. In the project we employ hydrogels (biomimetic polyurethanes, water-soluble and heat-sensitive) in which stem cells (embryonic or adult) are encapsulated. The scaffolds are tested in vitro, in order to assess their ability to host the cells.
Moreover we aim to inject scaffolds and stem cells in vivo, in a mouse model of spinal cord contusion. To evaluate the efficacy of the treatment, we intend to study sensorimotor performance of animals, the survival/integration of cells in the host tissue, and the expression of molecules involved in the regeneration and neuroinflammation.