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Current Protein & Peptide Science

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ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

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Perspective

Dephosphorylation Targeting Chimaera (DEPTAC): Targeting Tau Proteins in Tauopathies

Author(s): Andrea Soumbasis, Mohamed A. Eldeeb*, Mohamed A. Ragheb and Cornelia E. Zorca

Volume 23, Issue 3, 2022

Published on: 09 June, 2022

Page: [129 - 132] Pages: 4

DOI: 10.2174/1389203723666220519154229

Abstract

One salient hallmark of neurodegeneration is the accumulation of toxic protein aggregates in neuronal cells. This proteotoxicity culminates in the deterioration of neuronal function. In AD and related tauopathies, the microtubule-associated protein tau becomes hyperphosphorylated. Hyperphosphorylated tau forms neurofibrillary tangles (NFTs) within neurons, which constitute a unique feature of tauopathies, including AD. A recent study has exploited a novel molecular strategy to counteract hyperphosphorylated tau and enhance its degradation. Analogous to the PROTAC methodology, a novel dephosphorylation targeting chimera (DEPTAC) was designed to promote the molecular interaction between tau and phosphatase, which, in turn, augments its degradation. Herein, we briefly discuss this novel finding and its potential therapeutic implications.

Keywords: Protein degradation, protein quality control, Alzheimer's disease, neurodegeneration, tau, taupathies, targeted degradation, phsophorylation.

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