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Mechanisms of cell dysfunction by aggregation dynamics of polyQ-containing proteins

Final Report Summary - MECHAGGRENAMICS (Mechanisms of cell dysfunction by aggregation dynamics of polyQ-containing proteins)

Protein aggregation is a typical trait of a number of neurodegenerative diseases associated with aging. The genes responsible for modulating the aggregation are not completely known. There is an inverse correlation between the number of the CAG triplets within the huntingtin gene, and the age of onset of symptoms in patients of Huntington's disease (HD). However, there is a wide variation in age of onset of the disease, among carriers of short but toxic CAG tandems, which suggests that the genetic background of the patients strongly influences the severity of the disease.
In this proposal we have generate new in vivo models of HD to find molecules that modulate protein and RNA toxicity and disease progression. We also have tested several compound that reduce aggregation patterns, and also induce neuronal protection in contexes of polyQ toxicity.

We have found seeveral genes involved in protein toxicity dynamics, and also in genes that are involved in the toxicity produced by the nascent RNA containing expanded CAG triplets.

We are currently testing drugs against HD in a mice model of HD, the so-called zQ175. Some of these compounds will be considered for future clinical trials.

More information at the website of our lab: