PPARγ-coactivator-1α gene transfer reduces neuronal loss and amyloid-β generation by reducing β-secretase in an Alzheimer’s disease model
Open accessAbstract
Significance: The PPARγ-coactivator-1α (PGC-1α) is a transcriptional regulator of genes involved in energy metabolism. We observed previously that PGC-1α decreases the generation of Aβ in cell culture, and its levels are reduced in Alzheimer’s disease (AD) brains. To determine its potential therapeutic role in vivo, we delivered PGC-1α in specific brain areas of an AD model by using viral vectors. We found that PGC-1α–injected mice showed decreased Aβ plaques by reducing the expression of the main enzyme involved in Aβ production, preserving most neurons in the brain and performing as well as wild-type mice in cognitive tests. Therefore, PGC-1α selective delivery shows promising therapeutic value in AD.
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Treated mice showed better memory, no loss of brain cells in hippocampus and very few amyloid plaques after four months of injection.
“The treated mice showed better memory, no loss of brain cells in the hippocampus and had very few amyloid plaques after four months of injection.”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [102]
Untreated mice had multiple plaques in their brain.
“Those that had not been treated had multiple plaques in their brain [102].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [102]
Delivery of PGC1-alpha gene using a modified virus to brain cells of mice reduced development of Alzheimer's.
“In another study, scientists delivered a gene PGC1-alpha (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) using a modified virus to the brain cells of mice which reduced the development of Alzheimer's.”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [102]
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“Those that had not been treated had multiple plaques in their brain [102].”
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- Authors
- Katsouri, L., Lim, Y. M., Blondrath, K., Eleftheriadou, I., Lombardero, L., Birch, A. M., Mirzaei, N., Irvine, E. E., Mazarakis, N. D., & Sastre, M.
- Affiliations
- Imperial College London (GB)
- Medical Research Council (GB)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-10-10
- Volume
- 113
- Issue
- 43
- Pages
- 12292-12297
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5087021
- OpenAlex
- W2531769509
- Cited by
- 146
- References
- 43
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 15 · 2023: 14 · 2022: 17 · 2021: 24 · 2020: 17 · 2019: 14 · 2018: 15 · 2017: 8
- FWCI
- 9.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Alzheimer's Research UK (ART-PG2009-5, ARUK-ESG-2013-8)
- EC | European Research Council (23314)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- PGC-1α, Alzheimer's disease, amyloid-beta, BACE1, gene transfer, lentiviral vectors, APP23 transgenic mice, neuroprotection, neuroinflammation, microglial activation, inflammatory cytokines, CA3 pyramidal cells, neurotrophic factors, memory impairment, mitochondrial biogenesis
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Alzheimer Disease, Animals, Gene Expression Regulation, Genetic Vectors, Humans, Memory, Mice, Transgenic, Lentivirus, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Pyramidal Cells, Amyloid Precursor Protein Secretases, Protein Aggregation, Pathological
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