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Huntington's disease: a domino effect triggered by mutant huntingtin
Huntington’s disease (HD) is an inherited neurodegenerative disorder that causes progressive motor and cognitive dysfunction. The disease is caused by the expansion of a polyglutamine (polyQ) stretch in a protein named huntingtin.
Cells in HD brains are profoundly affected at multiple levels, from gene transcription to vesicle trafficking, cell signaling, energy metabolism and mitochondrial and synaptic function. It is not clear how mutant huntingtin affects so many aspects of the cell physiology. Our research focuses on the molecular mechanisms underlying HD with the ultimate goal of identifying therapeutic targets to treat this devastating disorder.
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Gangliosides in brain health and in neurodegeneration
Gangliosides are glycosphingolipids (sugar-lipid molecules) highly enriched in the brain. Embedded in cell lipid bilayers, gangliosides modulate the activity of several membrane proteins and growth factor receptors, and play an important role in many cell signalling pathways and in normal brain functioning.
In spite of the large body of evidence that links gangliosides to brain health and diseases, our understanding of the functions of these molecules is still very limited.
Our laboratory and others have shown that a reduction of ganglioside levels occurs in HD and in Parkinson's disease (PD). Restoring normal GM1 levels protects HD cells from apoptosis, slows down neurodegeneration and restores normal behaviour in HD animal models. Other studies have shown that GM1 is also protective in PD.
We are investigating the underlying molecular mechanisms to uncover novel functions of gangliosides involved in normal cell physiology and neuropathology.
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