DEPhosphorylation TArgeting Chimaera (DEPTAC): Targeting Tau Proteins in Tauopathies

One salient hallmark of neurodegeneration is the accumulation of toxic protein aggregates in neuronal cells. As such, this proteotoxicity culminates in the deterioration of neuronal function. In AD and related tauopathies, the microtubule-associated protein tau becomes hyperphosphorylated. Hyperphos...

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Bibliographic Details
Published inCurrent protein & peptide science
Main Authors Soumbasis, Andrea, Eldeeb, Mohamed A, Ragheb, Mohamed A, Zorca, Cornelia E
Format Journal Article
LanguageEnglish
Published United Arab Emirates 01.01.2022
Subjects
Protein degradation
Alzheimer disease
Neurodegeneration
Targeted degradation
Tau
Protein quality control
Phsophorylation
Taupathies
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Summary:One salient hallmark of neurodegeneration is the accumulation of toxic protein aggregates in neuronal cells. As such, 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.
ISSN:1875-5550
DOI:10.2174/1389203723666220519154229