Dettagli: Institute of Protein Biochemistry, CNR.
Via P. Castellino, 111 - 80131 Napoli
2015 IBP Seminar Series
CNR Conference Room
Wednesday, October 28th, 2015 at 14:30
Dr. Vittorio Maglione
IRCCS Neuromed, Pozzilli, Isernia, Italy
"New perspectives into pathogenesis and treatment of Huntington's disease"
Host: Dr. Giovanni D'Angelo
Tel. 081-6132543; e-mail: g.dangelo@ibp.cnr.it
Huntington's disease (HD), the most common dominantly inherited neurodegenerative disorder is characterized by a progressive striatal and cortical neurodegeneration. The disease causing mutation is an expanded CAG trinucleotide repeats (>36 repeats) encoding a polyglutamine (polyQ) stretch in N-terminal region of huntingtin, a ubiquitous protein whose function is still unclear.
So far, many are the aberrant molecular mechanisms described to be associated with the disease, however much remains to be defined. Recently, for the first time, Dr Maglione’s group has described that sphingolipid (ganglioside) metabolism is also perturbed in HD. In particular, we have found a significant reduction of ganglioside GM1 levels in different preclinical models and also in HD patient-derived fibroblasts. Interestingly, the administration of such ganglioside was neuroprotective and exerted beneficial therapeutic effect in HD animal models.
New data indicate that lipid breakdown is not only restricted to ganglioside metabolism, but it also affects regulation of sphingosine-1-phosphate (S1P), a potent signaling sphingolipid that normally regulates a number of processes essential to cellular homeostasis, including cell viability, differentiation and motility.
Although still under investigation, the observed dysfunctional S1P metabolism supports the idea that S1P bio-availability may be reduced in HD and negatively affect neuronal survival. Coherently, pharmacological modulation of S1P metabolism/axis results to be beneficial in HD cells and highlights the therapeutic potential of either S1P or its related pathways.
To date, there exists a variety of molecules/drugs that selectively target S1P metabolism/axis, currently used in clinical trials for human disorders. Progress in the understanding of S1P biology in HD would definitely enhance therapeutic perspectives for the treatment of the disease, by taking advantage from the already available molecules and by promoting the development of new ones..
Dr Maria Rosaria Coscia & Stefania Mariggiò
Seminar Coordinators
Institute of Protein Biochemistry, CNR
Via P. Castellino, 111
80131 Naples Italy
Tel 0039 081 6132556/545 |