The Role of p53 in Alzheimer’s Disease: Impact on Tau Pathology



Tau, a microtubule-associated protein with multiple phosphorylation sites, regulates microtubule assembly and dynamics. The presence of neurofibrillary tangles (NFT), consisting of intracellular aggregates of hyperphosphorylated tau protein, is one of the defining clinico-pathological hallmarks of Alzheimer’s disease (AD). Enhanced expression of transcription factor p53 is also found in brain tissue of AD patients. Although p53 is mainly involved in DNA damage response, apoptosis, and senescence, it exerts a much broader repertoire of cellular functions including promotion of axonal outgrowth and differentiation of progenitor cells to neuronal phenotype. Over time, pathologically enhanced expression of p53 might promote sustained tau hyperphosphorylation, contributing to the formation of NFT and ultimately neuronal death. Glycogen synthase kinase-3β (GSK-3β), the principal tau kinase, interacts with p53 and promotes its transcriptional and non-transcriptional mode of action. In this chapter, current knowledge of p53/GSK-3β/tau interplay in AD is briefly summarized. A deeper understanding of these interactions may shed new light on the pathological mechanisms underlying AD and could lead to novel therapies to combat this devastating disease.


Alzheimer disease Tau p53 GSK-3β Apoptosis Neurodegeneration 


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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Laboratory for Molecular Neuropharmacology, Division of Molecular MedicineRuđer Bošković InstituteZagrebCroatia
  2. 2.Department of PsychologyCatholic University of CroatiaZagrebCroatia
  3. 3.Department for NeuroscienceCroatian Institute for Brain Research, University of Zagreb Medical SchoolZagrebCroatia

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