How are connexin and lysosomal mutations involved in neurodegeneration?

We are interested in understanding the molecular function of connexin channels and lysosomes in physiology and pathology of the nervous system, in particular related to  Charcot-Marie-Tooth and Parkinson’s diseases. Our investigation is conceived to attain groundbreaking findings using an innovative approach which combines Physics, Biology and Medicine.

The Bortolozzi lab is currently focusing on two main projects: (i) the study of connexin 32 (Cx32) protein, whose mutations cause the X-linked form of Charcot-Marie-Tooth peripheral neuropathy (CMTX1), a degenerative motor and sensory disorder for which there is no cure; (ii) the study of pathological variants of the gene encoding the beta-glucocerebrosidase (GBA) lysosomal enzyme, known to confer a 5- to 7-fold increased risk to develop Parkinson’s disease (new starting project).
Overview of the CMT1X project: since the first mutations were reported in 1993, over 450 different mutations associated with CMTX1 have been identified in the GJB1 gene, which encodes Cx32. Despite the availability of numerous studies of normal and mutant Cx32 investigated under a variety of conditions, the molecular function of Cx32 channels in health and disease of the peripheral nervous remains unknown. Bortolozzi lab’s research points towards clarifying this function by (i) a combination of in silico, in vitro and in vivo techniques; (ii) cellular models based on human stem cells to mimic the peripheral nervous system as well as CMTX1 features; (iii) therapeutic strategies investigated at the single Cx32 channel level. We recently suggested a possible key role of Cx32 hemichannels in the molecular pathogenesis of CMTX1 and proposed a therapeutic strategy based on mimetic peptides (Carrer et al., Human Molecular Genetics, 2017).

Open position for the Parkinson's disease project View open position

MARIO BORTOLOZZI

  • Master Degree: Physics, University of Padova, Italy (2004).
  • PhD: Neurobiology, Biosciences School, University of Padova, Italy (2008).
  • Postdoc: Venetian Institute of Molecular Medicine (VIMM), Padova, Italy (2008-2010).
  • Assistant Professor: Dept. Physics and Astronomy, University of Padova, Italy (2010-2017).
  • Visiting Scientist: Dept. of Physiology, Anatomy and Genetics, University of Oxford, UK (2012-2013).
  • Group leader: Venetian Institute of Molecular Medicine (VIMM), Padova, Italy (since 2013).
  • Associate professor: Dept. Physics and Astronomy, University of Padova, Italy (since 2017).