Mechanistic pathopathway linking UCHL1 in HD. Literature and experimental findings are integrated to link proteins modulated by the expression of PolyQ Htt with intracellular pathways. As a starting point, an HD pathway from the Panther pathway database http://www.pantherdb.org/ was used and subsequently enriched with proteins and events functionally involved in cellular processes linked to neurodegeneration using CellDesigner http://celldesigner.org/. Inside the nucleus of HD patients, the mutant PolyQ Htt gene is transcribed into a messenger RNA with a potential stem secondary structure . Intranuclear aggregation of PolyQ Htt sequesters proteins binding to PolyQ Htt, including CBP, hence reducing the cAMP response element-mediated transcription of the CREB-target genes . UCHL1 was reported to potentiate CREB-target genes transcription by restoring normal proteasomal degradation of the PKA-regulatory subunit II alpha (PKA-r), PKA activity (PKA-c), and CREB phosphorylation, hence resulting in contextual memory retrieval .