AFM-TELETHON - 23786 - POST-DOCTORAL FELLOWSHIPS - PHENOTIPIC EVALUATION OF MICROTUBULES NETWORK AS PROGNOSTIC AND PREDICTIVE MARKER IN RESPONSE TO SPASTIN ELEVATING APPROACHES IN HEREDITARY SPASTIC PARAPLEGIA TYPE 4 (DSB.AD006.337)
Area tematica
Area progettuale
Biologia Molecolare/Cellulare (DSB.AD006)Struttura responsabile del progetto di ricerca
Istituto di biologia e patologia molecolari (IBPM)
Responsabile di progetto
FRANCESCA SARDINA
Telefono: 0649917537
E-mail: francesca.sardina3@gmail.com
Abstract
The most common type of Hereditary Spastic Paraplegia (HSP) is due to autosomal dominant mutations in the SPG4gene, encoding spastin, a microtuble (MT) severing protein. We found that the kinase HIPK2 regulates spastin stability. HIPK2 overexpression/activation increases spastin levels in SPG4-HSP cells and rescues neurite defects in a spastin-deficient cell model, suggesting that manipulation of HIPK2/spastin axis is a strategy to develop spastin-elevating therapeutic approaches. I observed peculiar MT network defects in SPG4-HSP lymphoblastoid cells that were rescued by increasing pharmacologically spastin protein levels. Here, I propose to analyze and deeply characterize MT network architecture in peripheral-blood lymphocytes from SPG4-HSP patient families, in order to establish a correlation between the observed defects and the severity of the disease. Additionally, I will characterize MT network architecture in response to spastin elevating approach in the same experimental system. The main goals of this proposal will be to obtain a prognostic, non-invasive method for SPG4-HSP and to set up an experimental system to predict the effectiveness of therapeutic treatments.
Obiettivi
1. Analyze MT cytoskeleton network in SPG4-HSP and its relationship with molecular and clinical patient features.
2. Evaluate the effect of spastin elevating approaches on MT cytoskeleton network in SPG4-HSP patient derived cells
Data inizio attività
01/01/2022
Parole chiave
Hereditary Spastic Paraplegia (HSP), Spastin, Microtubules
Ultimo aggiornamento: 16/04/2024