Cited by 126Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

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Nuclear receptors as therapeutic targets for Alzheimer's disease

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Mandrekar-Colucci, Shweta, Landreth, Gary E·2011·Expert Opinion on Therapeutic Targets

DOI 10.1517/14728222.2011.594043PMC PMC3156324

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Abstract

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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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
DOI: 10.1517/14728222.2011.594043
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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Nuclear receptors as therapeutic targets for Alzheimer's disease

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