Linea 1 – Biomarcatori diagnostici e prognostici

La linea di ricerca 1 mira alla comprensione delle basi fisiopatologiche e genetiche implicate in molteplici patologie neurologiche, malattie rare e neuromuscolari.

Essa utilizza tecniche di neuroimmagini, cosi come di biologia molecolare, al fine di individuare i fattori di suscettibilità alle patologie neurologiche nonché dell’identificazione di nuovi biomarcatori di rilevanza diagnostica e prognostica.

Vengono studiati i meccanismi neurobiologici e neurometabolici che sono alla base delle malattie neuromuscolari e neurodegenerative.

Al fine di portare avanti le suddette ricerche, la linea di ricerca si avvale del supporto principale dei Laboratori di Neuroimmagini e di Biologia Clinica.

Contatti del Responsabile di Linea

Dante Mantini

Dante Mantini

Responsabile Linea 1 - Biomarcatori Diagnostici e Prognostici

Progetti di ricerca:

Cell cultures and in vitro models for the study of rare diseases

Corrado Angelini

2018-

36 mesi

Linea di ricerca:

BIOMARCATORI DIAGNOSTICI E PROGNOSTICI

Altre strutture coinvolte:

Biobank BBMRNR

Altri enti coinvolti:

Università di Bologna, Università Cattolica di Milano, Università degli Studi di Padova, TIGEM di Napoli, Dip. Neurology of Budapest

Tipo di grant:

Ricerca corrente

Ente finanziatore:

Ministero della salute

The study on the accumulation of neutral lipids in fibroblasts of NLSD-M, starting with the Telethon project (GGP14066) will be continued. Experiments will be carried out on fibroblast cultures and iPSC cells in metabolic diseases by testing pharmacological agents for the reduction of lipid accumulation. New mutations in lipid diseases will be sought from ETFDH defect and in other cases of lipid myopathies. We will use engineered myoblast and fibroblasts cultures as a model for the study of the mechanisms that lead to this pathology, in particular investigating the role of TNPO3 in muscle.

Neuroimaging and evolution of the cognitive profile in Myotonic Dystrophies Type 1

Corrado Angelini

2018-

36 mesi

Linea di ricerca:

BIOMARCATORI DIAGNOSTICI E PROGNOSTICI

Altre strutture coinvolte:

Neuroimage Lab, Dept. of Neuropsychology

Altri enti coinvolti:

Servizio di Neuroradiologia Azienda Ospedaliera Pisana, Laboratorio di Neuropsicologia Azienda Ospedaliera Pisana, Registro UILDM di Venezia e Nazionale

Tipo di grant:

Ricerca corrente

Ente finanziatore:

Ministero della salute

In neuroimaging studies, widespread brain alterations, such as general atrophy, reduction of the volume of gray matter in all four lobes and the cerebellum have been documented. The prevalence of hyperintensities localized in white matter is estimated to be around 70% in DM1. Tractography analysis shows an increase in mean diffusivity in all four lobes and a reduction of fractional anisotropy in the main white matter traits. Functional studies also demonstrate a reduced capacity of glucose uptake and cerebral perfusion in the frontal, parietal, and temporal lobes and anomalous connectivity observed by fMRI. However, the significant differences emerged in the different studies are obtained with the use of different brain imaging methods. Moreover, we would like to determine if differences found are due to a developmental or to a neuronal degenerative process.

Novel therapeutic targets in Parkinson's disease (Nuovi bersagli terapeutici nella Malattia di Parkinson)

Laura Civiero

2020-2022

36 mesi

Linea di ricerca:

BIOMARCATORI DIAGNOSTICI E PROGNOSTICI

Altre strutture coinvolte:

Unità di fisiologia cellulare e molecolare, Dipartimento di Biologia, Università di Padova

Altri enti coinvolti:

Università di Padova

Tipo di grant:

Ricerca Finalizzata, Giovani Ricercatori (GR-2016-02363461)

Ente finanziatore:

Ministero della Salute

Parkinson’s disease (PD) is a common, severe neurodegenerative disorder with unknown etiology and without cure. The study of genes mutated in familial forms of PD with pathological and clinical overlap with the sporadic syndrome gives us the opportunity to unravel novel molecular mechanisms of such a complex disorder. By studying PD-linked proteins and the related signalling pathways, we identified a number of aberrantly regulated targets both in PD cellular systems and in PD mouse models. Within this project, we will investigate the activation status of these molecules in human biological samples from PD patients with the aim of validating a set of biomarkers in PD.

 

La malattia di Parkinson (MP) è un disturbo neurodegenerativo comune molto grave con eziologia sconosciuta e senza cura. Lo studio di geni mutati in forme familiari di MP con sovrapposizione patologica e clinica alla sindrome sporadica ci dà l’opportunità di svelare nuovi meccanismi molecolari di un disturbo così complesso. Investigando le proteine coinvolte nella MP a carattere genetico e le relative vie di segnalazione, abbiamo identificato un numero di target regolati in modo aberrante sia in sistemi cellulari che in modelli murini di MP. Nell’ambito di questo progetto, stiamo validando lo stato di attivazione di queste molecole in campioni biologici umani di pazienti con MP con l’obiettivo di convalidare una serie di biomarcatori nella MP.

Pathogenesis of muscular dystrophies: role of atrophy and autophagy and correlations with muscular MRI

Corrado Angelini

2017-

36 mesi

 

Linea di ricerca:

BIOMARCATORI DIAGNOSTICI E PROGNOSTICI

 

Altre strutture coinvolte:

Biobanca BBMRNR

Altri enti coinvolti:

Università di Bologna, Università di Modena, registri nazionali: FSHD, GSD, Distrofinopatie, Unipd.

 

Tipo di grant:

Ricerca corrente

 

Ente finanziatore:

Ministero della salute

 

The project aims are to identify patients with unknown myopathies by genetic analysis, to follow-up with MRI quantified using Mercuri score muscle evolution and compare it with functional status of patients such as GSGC scale. We expect to verify consistent finding between GSGC score, muscle imaging and other parameters as muscle groups muscle MRC score.

Study of lipid storage diseases by imaging and cellular models

Corrado Angelini

2018-

36 mesi

Linea di ricerca:

BIOMARCATORI DIAGNOSTICI E PROGNOSTICI

Altre strutture coinvolte:

Biobank BBMRNR

Altri enti coinvolti:

Università Cattolica di Milano, Università di Roma

Tipo di grant:

Ricerca corrente

Ente finanziatore:

Ministero della salute

We propose to investigate the serum molecular biomarkers that reflect the consequence of muscle atrophy and to observe the changes in level expression of microRNAs and correlate them with the MRI analysis. Furthermore, the medical genetic staff of the University of Milano will help us in this study with the fibroblast culture of these patients for the future study. New therapies could be found by understanding the mechanism of muscle atrophy and cellular content of triglycerides.

Study of the pathogenesis of Neurodegenerative Diseases and mitochondrial involvement

Corrado Angelini

2018-

36 mesi

Linea di ricerca:

BIOMARCATORI DIAGNOSTICI E PROGNOSTICI

Altre strutture coinvolte:

Biobank BBMRNR

Altri enti coinvolti:

Dept of Genetics and Biology, University of Padova

Tipo di grant:

Ricerca corrente

Ente finanziatore:

Ministero della salute

We propose to observe the changes in the level expressions of microRNAs that they might influence the mitochondrial metabolism by acting on it; in fact, they could increase the production of ROS, or modulate the expression of specific genes by increasing apoptosis. We studied the regulation of Er- mitochondria contact by Parkin in parkin mutant fibroblasts and in Drosophila models. We also would like to investigate the role of OX/PHOS proteins complexes and the alterations of production of cytochrome oxidase complex. MicroRNAs could be a valid biomarker for investigating the damage in hearing pathways and in several mitochondrial diseases. Future researchers could be needed for testing these biomarkers in prospective human clinical studies.

Tissue, molecular and protein biomarkers in rare, neuromuscular and neurodegenerative diseases (ALS)

Corrado Angelini

2018-

36 mesi

Linea di ricerca:

BIOMARCATORI DIAGNOSTICI E PROGNOSTICI

Altre strutture coinvolte:

Biobank BBMRNR, Spine lesion Unit, ALS Unit, Neuroncological diseases Unit

Altri enti coinvolti:

University of Padova, Associazione beta-sarcoglicanopatie e ad altre associazioni (UILDM e Jain-Foundation)

Tipo di grant:

Ricerca corrente

Ente finanziatore:

Ministero della salute

The study on biopsies of patients with genetic ALS (with mutations in C9orf, SOD1 gene) and sporadic has the aim to highlight the tissue-related differences of microRNA and protein expression and compared it with clinical features. We propose to investigate the circulating miRNAs in patients affected by several conditions and their correlation with muscle atrophy and clinical/instrumental evaluation. The effects of rehabilitation in patients with ALS, DM1, and Hereditary Spastic Paraparesis hospitalized in our center is one of our specific aim: a multidisciplinary approach based on molecular and protein biomarkers, clinical parameters and outcome scales will be done.