PMID- 33256579
OWN - NLM
STAT- MEDLINE
DCOM- 20211104
LR  - 20211104
IS  - 1875-5828 (Electronic)
IS  - 1567-2050 (Linking)
VI  - 17
IP  - 11
DP  - 2020
TI  - IL-8 and MCP-1 Impact on Tau Phosphorylation and Phosphatase Activity.
PG  - 985-1000
LID - 10.2174/1567205017666201130091129 [doi]
AB  - BACKGROUND: Chronic inflammation is a feature of Alzheimer s disease (AD), 
      resulting in excessive production of inflammatory mediators that can lead to 
      neuroinflammation, contributing to alterations in Abeta production and deposition as 
      Senile Plaques (SPs), and to neurofibrillary tangles (NFTs) formation, due to 
      hyperphosphorylated Tau protein. OBJECTIVE: This work addressed the impact of the 
      interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), two 
      chemokines, on Tau phosphorylation; and also evaluated the chemokines' levels in 
      plasma using samples from a regional cohort. METHODS: Human neuronal SH-SY5Y 
      cells exposed to IL-8 and MCP-1 chemokines were monitored for their protein and 
      phosphorylated protein levels by western blotting analysis. A serine/threonine 
      protein phosphatase (PPs) activity assay was employed to monitor PPs activity. 
      Subsequently, flow cytometry was used to monitor chemokines levels in plasma 
      samples from individuals with cognitive deficits. RESULTS: Chemokines' exposure 
      resulted only in minor cytotoxicity effects on SH-SY5Y, and in increased Tau 
      phosphorylation, particularly at the S396 residue. Tau phosphorylation correlated 
      with PPs inhibition and was consistent with GSK3beta phosphorylation-mediated 
      inhibition. Subsequent analysis of plasma from individuals with cognitive 
      deficits showed that IL-8 levels were decreased. CONCLUSION: Data shows that both 
      chemokines tested can exert an effect on GSK3beta phosphorylation and modulate PPs 
      activity, potentially resulting in increased Tau phosphorylation and subsequent 
      NFTs formation. One can deduce that increased chemokines stimulation during 
      chronic inflammation can exacerbate this event. The work contributes to a better 
      understanding of the mode of action of these chemokines on AD pathogenesis and 
      opens novel research avenues.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Vaz, Margarida
AU  - Vaz M
AD  - Neurosciences and Signalling Group, Institute of Biomedicine, Department of 
      Medical Sciences, University of Aveiro, Aveiro, Portugal.
FAU - Domingues, Catarina
AU  - Domingues C
AD  - Neurosciences and Signalling Group, Institute of Biomedicine, Department of 
      Medical Sciences, University of Aveiro, Aveiro, Portugal.
FAU - Trindade, Dario
AU  - Trindade D
AD  - Neurosciences and Signalling Group, Institute of Biomedicine, Department of 
      Medical Sciences, University of Aveiro, Aveiro, Portugal.
FAU - Barra, Catia
AU  - Barra C
AD  - Neurosciences and Signalling Group, Institute of Biomedicine, Department of 
      Medical Sciences, University of Aveiro, Aveiro, Portugal.
FAU - Oliveira, Joana M
AU  - Oliveira JM
AD  - Neurosciences and Signalling Group, Institute of Biomedicine, Department of 
      Medical Sciences, University of Aveiro, Aveiro, Portugal.
FAU - Rosa, Ilka M
AU  - Rosa IM
AD  - Neurosciences and Signalling Group, Institute of Biomedicine, Department of 
      Medical Sciences, University of Aveiro, Aveiro, Portugal.
FAU - da Cruz E Silva, Odete A B
AU  - da Cruz E Silva OAB
AD  - Neurosciences and Signalling Group, Institute of Biomedicine, Department of 
      Medical Sciences, University of Aveiro, Aveiro, Portugal.
FAU - Henriques, Ana G
AU  - Henriques AG
AD  - Neurosciences and Signalling Group, Institute of Biomedicine, Department of 
      Medical Sciences, University of Aveiro, Aveiro, Portugal.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Alzheimer Res
JT  - Current Alzheimer research
JID - 101208441
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 0 (tau Proteins)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
SB  - IM
MH  - Alzheimer Disease/pathology
MH  - Chemokine CCL2/*blood
MH  - Cognition Disorders/pathology
MH  - Humans
MH  - Interleukin-8/*blood
MH  - Phosphoric Monoester Hydrolases/*metabolism
MH  - Phosphorylation/*physiology
MH  - Plaque, Amyloid/pathology
MH  - tau Proteins/*metabolism
OTO - NOTNLM
OT  - Alzheimer s disease
OT  - Chemokines
OT  - IL-8
OT  - MCP-1
OT  - kinases
OT  - phosphatases
OT  - tau
EDAT- 2020/12/02 06:00
MHDA- 2021/11/05 06:00
CRDT- 2020/12/01 05:35
PHST- 2020/03/31 00:00 [received]
PHST- 2020/10/03 00:00 [revised]
PHST- 2020/10/06 00:00 [accepted]
PHST- 2020/12/02 06:00 [pubmed]
PHST- 2021/11/05 06:00 [medline]
PHST- 2020/12/01 05:35 [entrez]
AID - CAR-EPUB-111925 [pii]
AID - 10.2174/1567205017666201130091129 [doi]
PST - ppublish
SO  - Curr Alzheimer Res. 2020;17(11):985-1000. doi: 10.2174/1567205017666201130091129.