Author: Seneci, Pierfausto
Title: Targeting Proteasomal Degradation of Soluble, Misfolded Proteins: Ubi Major… Cord-id: to6v3cft Document date: 2015_1_23
ID: to6v3cft
Snippet: This chapter deals with small molecule modulators of the ubiquitin–proteasome system (UPS). They are designed to restore its impaired capacity to dispose of soluble, dysfunctional protein copies, and to fight its pathological impairment in proteinopathies in general and in tauopathies in particular. Two specific molecular targets belonging to the U-box E3 ligase family (C-terminus of Hsc70 interacting protein, CHIP) and to the proteasome-associated cysteine protease DUB family (USP14) are sele
Document: This chapter deals with small molecule modulators of the ubiquitin–proteasome system (UPS). They are designed to restore its impaired capacity to dispose of soluble, dysfunctional protein copies, and to fight its pathological impairment in proteinopathies in general and in tauopathies in particular. Two specific molecular targets belonging to the U-box E3 ligase family (C-terminus of Hsc70 interacting protein, CHIP) and to the proteasome-associated cysteine protease DUB family (USP14) are selected for their putative role against NDDs and tauopathies. The limited available structural information for the two targets, and for their interactions with members of UPS-driven protein complexes, is described. A small number of known modulators for each target (or even for structurally related targets, possibly to provide translatable examples) are portrayed in terms of their biological profile, and of their development potential as disease-modifying drugs against NDDs.
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