Project 2

Early clinical features of Huntington’s disease (HD) include cognitive impairment and psychiatric manifestations. These early aspects of the disease have been attributed, in part, to a reduction in neurotransmitters and synaptic proteins levels. Molecular and cellular aspects of HD are characterized by aggregation of the mutated Huntingtin (mHtt) proteins into inclusion bodies, associated with deficits in proteasomal degradation.

In this project we will use neuronal cell cultures to characterize selective synaptic dysfunctions that might by associated with early HD pathology by co-expressing exon one of the w.t or the mHtt gene together with synaptic reporters. We will also apply different pharmacological agents that affect Ubiquitin Proteasome System dependent protein degradation to test the involvement of the UPS in HD pathology.