Alzheimer’s disease and tau self-assembly: in the search of the missing link
Author
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González, Andrea
Author
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Singh, Sandeep Kumar
Author
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Churruca Muñoz, Macarena
Author
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Maccioni Baraona, Ricardo Benjamín
Admission date
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2022-06-03T19:10:51Z
Available date
dc.date.available
2022-06-03T19:10:51Z
Publication date
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2022
Cita de ítem
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Int. J. Mol. Sci. 2022, 23, 4192
es_ES
Identifier
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10.3390/ijms23084192
Identifier
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https://repositorio.uchile.cl/handle/2250/185840
Abstract
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Alzheimer's disease (AD) is a multifactorial neurodegenerative disease characterized by progressive cognitive impairment, apathy, and neuropsychiatric disorders. Two main pathological hallmarks have been described: neurofibrillary tangles, consisting of tau oligomers (hyperphosphorylated tau) and A beta plaques. The influence of protein kinases and phosphatases on the hyperphosphorylation of tau is already known. Hyperphosphorylated tau undergoes conformational changes that promote its self-assembly. However, the process involving these mechanisms is yet to be elucidated. In vitro recombinant tau can be aggregated by the action of polyanions, such as heparin, arachidonic acid, and more recently, the action of polyphosphates. However, how that process occurs in vivo is yet to be understood. In this review, searching the most accurate and updated literature on the matter, we focus on the precise molecular events linking tau modifications, its misfolding and the initiation of its pathological self-assembly. Among these, we can identify challenges regarding tau phosphorylation, the link between tau heteroarylations and the onset of its self-assembly, as well as the possible metabolic pathways involving natural polyphosphates, that may play a role in tau self-assembly.
es_ES
Patrocinador
dc.description.sponsorship
FONDEF project of ANID, Chile ID19I10301
Ricardo Benjamin Maccioni Foundation
International Center for Biomedicine
es_ES
Lenguage
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en
es_ES
Publisher
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MDPI
es_ES
Type of license
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Attribution-NonCommercial-NoDerivs 3.0 United States