Imperial College London
Alternate

ProfessorRichardFestenstein

Faculty of Medicine, Department of Brain Sciences

Clinical Professor of Molecular Medicine
 
 
 
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Contact

 

+44 (0)20 3313 8310r.festenstein

 
 
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Assistant

 

Ms Hyacinth Henry +44 (0)20 3313 3172

 
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Location

 

London Institute of Medical Sciences, Mansfield BuildingNeptune BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ng:2020:10.1038/s41380-020-0701-0,
author = {Ng, RC-L and Jian, M and Ma, OK-F and Bunting, M and Kwan, JS-C and Zhou, G-J and Senthilkumar, K and Iyaswamy, A and Chan, P-K and Li, M and Leung, KM-Y and Kumar, Durairajan S-S and Lam, KS-L and Chu, L-W and Festenstein, R and Chung, SK and Chan, K-H},
doi = {10.1038/s41380-020-0701-0},
journal = {Molecular Psychiatry},
title = {Chronic oral administration of adipoRon reverses cognitive impairments and ameliorates neuropathology in an Alzheimer's disease mouse model},
url = {http://dx.doi.org/10.1038/s41380-020-0701-0},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Circulating adiponectin (APN) levels decrease with age and obesity. On the other hand, a reduction in APN levels is associated with neurodegeneration and neuroinflammation. We previously showed that aged adiponectin knockout (APN−/−) mice developed Alzheimer’s like pathologies, cerebral insulin resistance, and cognitive impairments. More recently, we also demonstrated that APN deficiency increased Aβ-induced microglia activation and neuroinflammatory responses in 5xFAD mice. There is compelling evidence that deregulated insulin activities or cerebral insulin resistance contributes to neuroinflammation and Alzheimer’s disease (AD) pathogenesis. Here, we demonstrated that APN levels were reduced in the brain of AD patients and 5xFAD mice. We crossbred 5xFAD mice with APN−/− mice to generate APN-deficient 5xFAD (5xFAD;APN−/−). APN deficiency in 5xFAD mice accelerated amyloid loading, increased cerebral amyloid angiopathy, and reduced insulin-signaling activities. Pharmacokinetics study demonstrated adipoRon (APN receptor agonist) was a blood–brain barrier penetrant. AdipoRon improved neuronal insulin-signaling activities and insulin sensitivity in vitro and in vivo. Chronic adipoRon treatment improved spatial memory functions and significantly rescued neuronal and synaptic loss in 5xFAD and 5xFAD;APN−/− mice. AdipoRon lowered plaque and Aβ levels in AD mice. AdipoRon also exerted anti-inflammatory effects by reducing microglial and astrocytes activation as well as suppressing cerebral cytokines levels. The microglial phagocytic activity toward Aβ was restored after adipoRon treatment. Our results indicated that adipoRon exerts multiple beneficial effects providing important therapeutic implications. We propose chronic adipoRon administration as a potential treatment for AD.
AU  - Ng,RC-L
AU  - Jian,M
AU  - Ma,OK-F
AU  - Bunting,M
AU  - Kwan,JS-C
AU  - Zhou,G-J
AU  - Senthilkumar,K
AU  - Iyaswamy,A
AU  - Chan,P-K
AU  - Li,M
AU  - Leung,KM-Y
AU  - Kumar,Durairajan S-S
AU  - Lam,KS-L
AU  - Chu,L-W
AU  - Festenstein,R
AU  - Chung,SK
AU  - Chan,K-H
DO  - 10.1038/s41380-020-0701-0
PY  - 2020///
SN  - 1359-4184
TI  - Chronic oral administration of adipoRon reverses cognitive impairments and ameliorates neuropathology in an Alzheimer's disease mouse model
T2  - Molecular Psychiatry
UR  - http://dx.doi.org/10.1038/s41380-020-0701-0
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000518096200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41380-020-0701-0#Abs1
ER  -
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