The DOI matches its Crossref record; 110 of the 112 references it cites were found in a registry or an index.
Nuclear receptors as therapeutic targets for Alzheimer's disease
Open accessAbstract
INTRODUCTION: Alzheimer's disease (AD) is characterized by the accumulation and extensive deposition of amyloid β (Aβ) in the parenchyma of the brain. This accumulation of amyloid is associated with perturbations in synaptic function, impairments in energy metabolism and induction of a chronic inflammatory response which acts to promote neuronal loss and cognitive impairment. AREAS COVERED: Currently, there are no drugs that target the underlying mechanisms of AD. Here, we propose a class of nuclear receptors as novel and promising new therapeutic targets for AD. This review summarizes the literature on nuclear receptors and their effects on AD-related pathophysiology. EXPERT OPINION: Nuclear receptors are attractive targets for the treatment of AD due to their ability to facilitate degradation of Aβ, affect microglial activation and suppress the inflammatory milieu of the brain. Liver X receptor agonists have proven difficult to move into clinical trials as long-term treatment results in hepatic steatosis. It is our view that PPAR-γ activation remains a promising avenue for the treatment for AD; however, the poor BBB permeability of the currently available agonists and the negative outcome of the Phase III clinical trials are likely to diminish interest in pursuing this target.
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“LXR is a member of a group of nuclear receptors, peroxisome proliferator-activated receptors (PPARs; other members are PPARγ and PPARδ), each of which upon activation heterodimerizes with retinoid X receptor (RXR) to form a functional transcription factor along with coactivators that act to regulate expression of many genes, including those involved in AD pathogenesis [34].”
From Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk (2023) · cites this paper as [34]
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“The independent associations of two APOE promoter SNPs (rs769446, rs405509) with ApoE level are most likely due to their close proximity to LXR/RXR response element, as APOE expression is regulated by LXR/RXR.”
From Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk (2023) · cites this paper as [34]
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“A number of studies of the thiazolidinedione agonists of PPARγ, pioglitazone (Actos) and rosiglitazone (Avandia), reported salutary effects of these drugs in murine models of AD (Mandrekar-Colucci and Landreth, 2011).”
From Mechanisms Underlying the Rapid Peroxisome Proliferator-Activated Receptor-γ-Mediated Amyloid Clearance and Reversal of Cognitive Deficits in a Murine Model of Alzheimer's Disease (2012) · cites this paper as Mandrekar-Colucci and Landreth, 2011
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Background
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Metadata
- Authors
- Mandrekar-Colucci, S., & Landreth, G. E.
- Affiliations
- Case Western Reserve University (US)
- Corresponding author
- Landreth, Gary E
- ORCID
- Landreth, Gary E
- Venue
- Expert Opinion on Therapeutic Targets
- Publisher
- Informa UK Limited
- Published
- 2011-07
- Volume
- 15
- Issue
- 9
- Pages
- 1085-1097
- ISSN
- 1472-8222 (ISSN-L)
- 1744-7631
- PMC
- PMC3156324
- OpenAlex
- W2151194854
- Cited by
- 126
- References
- 112
- Citations by year
- 2026: 9 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 5 · 2021: 9 · 2020: 4 · 2019: 8 · 2018: 8 · 2017: 5 · 2016: 9 · 2015: 9 · 2014: 10 · 2013: 20 · 2012: 10
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Expert Opinion on Therapeutic Targets (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (1-R01-AG030482, R01AG030482)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
- Alzheimer's disease, nuclear receptors, therapeutic target, amyloid-beta, PPARγ agonists, liver X receptor agonist, microglial activation, neuroinflammation, blood-brain barrier permeability, hepatic steatosis, drug development
- MeSH terms
- Alzheimer Disease, Animals, Brain, Energy Metabolism, Humans, Inflammation, Drug Design, Amyloid beta-Peptides, Drug Delivery Systems, Microglia, Receptors, Cytoplasmic and Nuclear
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