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2019 ; 2
(7
): 1800143
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PDZ Domains as Drug Targets
#MMPMID32313833
Christensen NR
; ?aly?eva J
; Fernandes EFA
; Lüchow S
; Clemmensen LS
; Haugaard-Kedström LM
; Strømgaard K
Adv Ther (Weinh)
2019[Jul]; 2
(7
): 1800143
PMID32313833
show ga
Protein-protein interactions within protein networks shape the human interactome,
which often is promoted by specialized protein interaction modules, such as the
postsynaptic density-95 (PSD-95), discs-large, zona occludens 1 (ZO-1) (PDZ)
domains. PDZ domains play a role in several cellular functions, from cell-cell
communication and polarization, to regulation of protein transport and protein
metabolism. PDZ domain proteins are also crucial in the formation and stability
of protein complexes, establishing an important bridge between extracellular
stimuli detected by transmembrane receptors and intracellular responses. PDZ
domains have been suggested as promising drug targets in several diseases,
ranging from neurological and oncological disorders to viral infections. In this
review, the authors describe structural and genetic aspects of PDZ-containing
proteins and discuss the current status of the development of small-molecule and
peptide modulators of PDZ domains. An overview of potential new therapeutic
interventions in PDZ-mediated protein networks is also provided.