Imperial College London
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ProfessorNicholasMazarakis

Faculty of Medicine, Department of Brain Sciences

Chair MolBioMedicine and Head of Gene Therapy
 
 
 
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Contact

 

+44 (0)20 7594 7024n.mazarakis Website

 
 
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Assistant

 

Mrs Hadeel Abdeen +44 (0)20 7594 7014

 
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Location

 

E402Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Katsouri:2016:10.1073/pnas.1606171113,
author = {Katsouri, L and Lim, YM and Blondrath, K and Eleftheriadou, I and Lombardero, L and Birch, AM and Mirzaei, N and Irvine, EE and Mazarakis, N and Sastre, M},
doi = {10.1073/pnas.1606171113},
journal = {Proceedings of the National Academy of Sciences of USA},
pages = {12292--12297},
title = {PPARγ-coactivator-1α gene transfer reduces neuronal loss and amyloid-β generation by reducing β-secretase in an Alzheimer’s disease model},
url = {http://dx.doi.org/10.1073/pnas.1606171113},
volume = {113},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Current therapies for Alzheimer’s disease (AD) are symptomatic and do not target the underlying Aβ pathology and other important hallmarks including neuronal loss. PPARγ-coactivator-1α (PGC-1α) is a cofactor for transcription factors including the peroxisome proliferator-activated receptor-γ (PPARγ), and it is involved in the regulation of metabolic genes, oxidative phosphorylation, and mitochondrial biogenesis. We previously reported that PGC-1α also regulates the transcription of β-APP cleaving enzyme (BACE1), the main enzyme involved in Aβ generation, and its expression is decreased in AD patients. We aimed to explore the potential therapeutic effect of PGC-1α by generating a lentiviral vector to express human PGC-1α and target it by stereotaxic delivery to hippocampus and cortex of APP23 transgenic mice at the preclinical stage of the disease. Four months after injection, APP23 mice treated with hPGC-1α showed improved spatial and recognition memory concomitant with a significant reduction in Aβ deposition, associated with a decrease in BACE1 expression. hPGC-1α overexpression attenuated the levels of proinflammatory cytokines and microglial activation. This effect was accompanied by a marked preservation of pyramidal neurons in the CA3 area and increased expression of neurotrophic factors. The neuroprotective effects were secondary to a reduction in Aβ pathology and neuroinflammation, because wild-type mice receiving the same treatment were unaffected. These results suggest that the selective induction of PGC-1α gene in specific areas of the brain is effective in targeting AD-related neurodegeneration and holds potential as therapeutic intervention for this disease.
AU  - Katsouri,L
AU  - Lim,YM
AU  - Blondrath,K
AU  - Eleftheriadou,I
AU  - Lombardero,L
AU  - Birch,AM
AU  - Mirzaei,N
AU  - Irvine,EE
AU  - Mazarakis,N
AU  - Sastre,M
DO  - 10.1073/pnas.1606171113
EP  - 12297
PY  - 2016///
SN  - 0027-8424
SP  - 12292
TI  - PPARγ-coactivator-1α gene transfer reduces neuronal loss and amyloid-β generation by reducing β-secretase in an Alzheimer’s disease model
T2  - Proceedings of the National Academy of Sciences of USA
UR  - http://dx.doi.org/10.1073/pnas.1606171113
UR  - http://hdl.handle.net/10044/1/58722
VL  - 113
ER  -
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