Phosphorylation of serine 305 in tau inhibits aggregation.
Aggregation
Antibody
Inhibition
Phosphorylation
Seeding
Tau
Journal
Neuroscience letters
ISSN: 1872-7972
Titre abrégé: Neurosci Lett
Pays: Ireland
ID NLM: 7600130
Informations de publication
Date de publication:
23 01 2019
23 01 2019
Historique:
received:
20
08
2018
revised:
30
10
2018
accepted:
06
11
2018
pubmed:
14
11
2018
medline:
22
6
2019
entrez:
14
11
2018
Statut:
ppublish
Résumé
Alzheimer's disease and other tauopathies are characterized by the brain accumulation of hyperphosphorylated aggregated tau protein forming pathological inclusions. Although elevated tau phosphorylated at many amino acid residues is a hallmark of pathological tau, some evidence suggest that tau phosphorylation at unique sites, especially within its microtubule-binding domain, might inhibit aggregation. In this study, the effects of phosphorylation of two unique residues within this domain, serine 305 (S305) and serine 320 (S320), were examined in the context of established aggregation and seeding models. It was found that the S305E phosphomimetic significantly inhibited both tau seeding and tau aggregation in this model, while S320E did not. To further explore S305 phosphorylation in vivo, a monoclonal antibody (2G2) specific for tau phosphorylated at S305 was generated and characterized. Consistent with inhibition of tau aggregation, phosphorylation of S305 was not detected in pathological tau inclusions in Alzheimer's disease brain tissue. This study indicates that phosphorylation of unique tau residues can be inhibitory to aggregate formation, and has important implications for potential kinase therapies. Additionally, it creates new tools for observing these changes in vivo.
Identifiants
pubmed: 30423399
pii: S0304-3940(18)30774-2
doi: 10.1016/j.neulet.2018.11.011
pmc: PMC6351168
mid: NIHMS1512962
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
MAPT protein, human
0
tau Proteins
0
Serine
452VLY9402
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
187-192Subventions
Organisme : NINDS NIH HHS
ID : L30 NS089022
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047266
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS089622
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS082168
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.
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