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Pathology, Prevention and Therapeutics of Neurodegenerative Disease pp 39–48Cite as

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

Abstract

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.

Keywords

  • Alzheimer disease
  • Tau
  • p53
  • GSK-3β
  • Apoptosis
  • Neurodegeneration

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Authors and Affiliations

  1. Laboratory for Molecular Neuropharmacology, Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia

    Maja Jazvinšćak Jembrek

  2. Department of Psychology, Catholic University of Croatia, Zagreb, Croatia

    Maja Jazvinšćak Jembrek

  3. Department for Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia

    Katy Newberg & Goran Šimić

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  1. Maja Jazvinšćak Jembrek
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Correspondence to Maja Jazvinšćak Jembrek .

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  1. Toxicology and Experimental Medicine Division, CSIR-Central Drug Research Institute, Lucknow, India

    Sarika Singh

  2. Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedar Sinai Medical Center, Los Angeles, CA, USA

    Dr. Neeraj Joshi

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Jembrek, M.J., Newberg, K., Šimić, G. (2019). The Role of p53 in Alzheimer’s Disease: Impact on Tau Pathology. In: Singh, S., Joshi, N. (eds) Pathology, Prevention and Therapeutics of Neurodegenerative Disease. Springer, Singapore. https://doi.org/10.1007/978-981-13-0944-1_4

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