Molecular underpinnings of neurodegenerative disorders: striatal-enriched protein tyrosine phosphatase signaling and synaptic plasticity

F1000Research
Paul J LombrosoAngus C Nairn

Abstract

This commentary focuses on potential molecular mechanisms related to the dysfunctional synaptic plasticity that is associated with neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Specifically, we focus on the role of striatal-enriched protein tyrosine phosphatase (STEP) in modulating synaptic function in these illnesses. STEP affects neuronal communication by opposing synaptic strengthening and does so by dephosphorylating several key substrates known to control synaptic signaling and plasticity. STEP levels are elevated in brains from patients with Alzheimer's and Parkinson's disease. Studies in model systems have found that high levels of STEP result in internalization of glutamate receptors as well as inactivation of ERK1/2, Fyn, Pyk2, and other STEP substrates necessary for the development of synaptic strengthening. We discuss the search for inhibitors of STEP activity that may offer potential treatments for neurocognitive disorders that are characterized by increased STEP activity. Future studies are needed to examine the mechanisms of differential and region-specific changes in STEP expression pattern, as such knowledge could lead to targeted therapies for disorders involving disrupted STE...Continue Reading

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Citations

Nov 10, 2018·Journal of Neurochemistry·Rika MotodateToshiharu Suzuki
Aug 21, 2019·Central Nervous System Agents in Medicinal Chemistry·Anurag K SinghGiriraj T Kulkarni
Sep 19, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Jordi Creus-Muncunill, Michelle E Ehrlich
Jan 19, 2020·The Journal of Biological Chemistry·Celeste RomeroLutz Tautz
Jul 28, 2020·International Journal of Molecular Sciences·Darya V TeleginaNataliya G Kolosova
Nov 12, 2020·Molecular Neurobiology·Efthalia AngelopoulouChristina Piperi
Jul 2, 2021·Frontiers in Cell and Developmental Biology·Yacoubou Abdoul Razak MahamanFeiqi Zhu

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Methods Mentioned

BETA
ubiquitination

Software Mentioned

STEP

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