New perspectives into pathogenesis and treatment of Huntington's disease

Il 28/10/2015 ore 14.30 - 15.30

Sala Conferenze CNR, Via P. Castellino, 111 Napoli

Dr Vittorio Maglione from IRCCS Neuromed (Pozzilli, Isernia) will give a seminar on the new perspectives into pathogenesis and treatment of Huntington’s disease.

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, we have 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 support 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 exist 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.

 

Organizzato da:
Ibp, Cnr

Referente organizzativo:
Giovanni D'Angelo
Cnr - Istituto di biochimica delle proteine
Via P. Castellino, 111 80131 Napoli
g.dangelo@ibp.cnr.it
081/6132543

Modalità di accesso: ingresso libero