ALBA DI PARDO

Dottoressa di ricerca

ciclo: XXXIII



Titolo della tesi: HUNTINGTON DISEASE: NEW INSIGTHS INTO PATHOGENESIS AND TREATMENT

ABSTRACT Huntington disease (HD) is a mid-life-onset neurodegenerative disorder characterized by involuntary movements, personality changes and dementia. It progresses to death within 10-20 years after onset. There is currently no cure to treat this fatal disease. In HD patients, the protein huntingtin (Htt) contains an abnormal expansion of a polyglutamine tract, which leads to the selective death of striatal and cortical neurons. The functions of huntingtin, as well as the dysfunctions induced by the mutation are still poorly understood, however, the mutation confers protein toxic gain-of-function effects resulting in a broad array of molecular and cellular dysfunctions either in central or peripheral tissues. This is coherent with the evidence that the disease, long described as a disorder purely of the brain, is increasingly recognized as multi-organ systemic condition. Evidence indicates that perturbations of lipid homeostasis represent an emerging disease feature in HD. In particular, impaired (glico)sphingolipid metabolism represents the most relevant perturbation, however much remains to be clarified on its role in HD pathology and how it may affect disease pathogenesis. Over the past years, we have contributed to demonstrate the alteration of sphingolipid metabolism represents a new hallmark of the disease and a common denominator among multiple HD models. In the studies presented in this thesis, I have tested the hypothesis that modulation of such a perturbed metabolism may be proposed as novel and more targeted therapeutic strategy to manage HD symptoms. From my perspective, what makes this hypothesis potentially promising in HD, is the evidence that drugs working through sphingolipid metabolism-related pathways are already in clinical trial for different other pathological conditions.

Produzione scientifica

  • 11573/1208182 - 2018 - The S1P Axis: New Exciting Route for Treating Huntington's Disease (01g Articolo di rassegna (Review))
    DI PARDO, ALBA; MAGLIONE, VITTORIO
  • 11573/1208178 - 2018 - Dissecting the Functional Consequences of De Novo DNA Methylation Dynamics in Human Motor Neuron Differentiation and Physiology (01a Articolo in rivista)
    DI PARDO, ALBA
  • 11573/1208189 - 2018 - Stimulation of S1PR5 with A-971432, a selective agonist, preserves blood-brain barrier integrity and exerts therapeutic effect in an animal model of Huntington's disease (01a Articolo in rivista)
    DI PARDO, ALBA; MADONNA, MICHELE; MAGLIONE, VITTORIO
  • 11573/1691707 - 2023 - Abnormal expression of sphingolipid-metabolizing enzymes in the heart of spontaneously hypertensive rat models (01a Articolo in rivista)
    PEPE, GIUSEPPE; COTUGNO, ENRICO MARIA; FORTE, MAURIZIO; STANZIONE, ROSITA; DI PARDO, ALBA; SCIARRETTA, SEBASTIANO; VOLPE, MASSIMO; RUBATTU, SPERANZA DONATELLA; MAGLIONE, VITTORIO
  • 11573/1208194 - 2018 - Positive Effects against UV-A Induced Damage and Oxidative Stress on an in Vitro Cell Model Using a Hyaluronic Acid Based Formulation Containing Amino Acids, Vitamins, and Minerals (01a Articolo in rivista)
    DI PARDO, ALBA; DE ROSA, MARIO
  • 11573/1350719 - 2019 - Curcumin dietary supplementation ameliorates disease phenotype in an animal model of Huntington's disease (01a Articolo in rivista)
    ROSA, PAOLO; MADONNA, MICHELE; CALOGERO, ANTONELLA; MAGLIONE, VITTORIO; DI PARDO, ALBA
  • 11573/1350709 - 2019 - Curcumin C3 complex®/Bioperine® has antineoplastic activity in mesothelioma: an in vitro and in vivo analysis (01a Articolo in rivista)
    MADONNA, MICHELE; DI PARDO, ALBA; MAGLIONE, VITTORIO
  • 11573/1350725 - 2019 - Mutant huntingtin interacts with the sterol regulatory element-binding proteins and impairs their nuclear import. (01a Articolo in rivista)
    DI PARDO, ALBA; MAGLIONE, VITTORIO
  • 11573/1350703 - 2019 - Stimulation of sphingosine kinase 1 (SPHK1) is beneficial in a Huntington's disease pre-clinical model (01a Articolo in rivista)
    DI PARDO, ALBA; MARRACINO, FRANCESCA MARIA; MADONNA, MICHELE; MAGLIONE, VITTORIO
  • 11573/1428964 - 2020 - Exosomes of Glioblastoma Present Higher Molecular Variation than a Tumor Primary Cell Line (01h Abstract in rivista)
    PACINI, LUCA; ROSA, PAOLO; BASTIANELLI, DANIELA; DI PARDO, ALBA; PIAZZA, AMEDEO; PETROZZA, VINCENZO; STOPPACCIARO, ANTONELLA; VECCHIONE, ANDREA; MISCUSI, MASSIMO; RACO, ANTONINO
  • 11573/1350715 - 2019 - Acute manganese treatment restores defective autophagic cargo loading in Huntington's disease cell lines. (01a Articolo in rivista)
    DI PARDO, ALBA; MAGLIONE, VITTORIO
  • 11573/1208187 - 2018 - New therapeutic drugs from bioactive natural molecules: The role of gut microbiota metabolism in neurodegenerative diseases (01a Articolo in rivista)
    DI PARDO, ALBA; MAGLIONE, VITTORIO
  • 11573/1655264 - 2022 - Polysialic acid sustains the hypoxia-induced migration and undifferentiated state of human glioblastoma cells (01a Articolo in rivista)
    ROSA, PAOLO; SCIBETTA, SOFIA; MANGINO, GIORGIO; FAZI, FRANCESCO; PETROZZA, VINCENZO; DI PARDO, ALBA; CALOGERO, ANTONELLA
  • 11573/1657085 - 2022 - Decipher non-canonical SPAST splicing mutations with the help of functional assays in patients affected by spastic paraplegia 4 (SPG4) (01f Lettera, Nota)
    FERESE, ROSANGELA; SUPPA, ANTONIO; ASCI, FRANCESCO; ZAMPOGNA, ALESSANDRO; D'ALESSIO, CARMELO; DI PARDO, ALBA
  • 11573/1208191 - 2018 - Sphingolipid metabolism: A new therapeutic opportunity for brain degenerative disorders (01g Articolo di rassegna (Review))
    DI PARDO, ALBA; MAGLIONE, VITTORIO

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