4.7 Review

14-3-3 Proteins: Novel Pharmacological Targets in Neurodegenerative Diseases

Journal

TRENDS IN PHARMACOLOGICAL SCIENCES
Volume 42, Issue 4, Pages 226-238

Publisher

CELL PRESS
DOI: 10.1016/j.tips.2021.01.001

Keywords

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Funding

  1. National Institutes of Health (NIH) [R01 NS088533, R01 NS112203, R56 NS115767, P50 NS108675]

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14-3-3 proteins are a family of proteins expressed throughout the body that are involved in various diseases. Despite the challenges in targeting their interactions, recent advances have made it possible to develop compounds that target 14-3-3 interactions with therapeutic implications for neurodegenerative disorders. Challenges still remain in optimizing specificity and target engagement to avoid unintended negative consequences.
14-3-3 proteins are a family of proteins expressed throughout the body and implicated in many diseases, from cancer to neurodegenerative disorders. While these proteins do not have direct enzymatic activity, they form a hub for many signaling pathways via protein-protein interactions (PPIs). 14-3-3 interactions have proven difficult to target with traditional pharmacological methods due to the unique nature of their binding. However, recent advances in compound development utilizing a range of tools, from thermodynamic binding site analysis to computational molecular modeling techniques, have opened the door to targeting these interactions. Compounds are already being developed targeting 14-3-3 interactions with potential therapeutic implication for neurodegenerative disorders, but challenges still remain in optimizing specificity and target engagement to avoid unintended negative consequences arising from targeting 14-3-3 signaling networks.

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