Pathways to Parkinson’s disease: a spotlight on 14-3-3 proteins

E. Giusto, T. A. Yacoubian, E. Greggio, L. Civiero

Research output: Contribution to journalReview articlepeer-review


14-3-3s represent a family of highly conserved 30 kDa acidic proteins. 14-3-3s recognize and bind specific phospho-sequences on client partners and operate as molecular hubs to regulate their activity, localization, folding, degradation, and protein–protein interactions. 14-3-3s are also associated with the pathogenesis of several diseases, among which Parkinson’s disease (PD). 14-3-3s are found within Lewy bodies (LBs) in PD patients, and their neuroprotective effects have been demonstrated in several animal models of PD. Notably, 14-3-3s interact with some of the major proteins known to be involved in the pathogenesis of PD. Here we first provide a detailed overview of the molecular composition and structural features of 14-3-3s, laying significant emphasis on their peculiar target-binding mechanisms. We then briefly describe the implication of 14-3-3s in the central nervous system and focus on their interaction with LRRK2, α-Synuclein, and Parkin, three of the major players in PD onset and progression. We finally discuss how different types of small molecules may interfere with 14-3-3s interactome, thus representing a valid strategy in the future of drug discovery.

Original languageEnglish
Article number85
Number of pages14
Journalnpj Parkinson's Disease
Issue number1
Publication statusPublished - Sept 21 2021

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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