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Significance of NF-κB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer’s disease and multiple sclerosis
Open accessAbstract
INTRODUCTION: Advances in molecular pathogenesis suggest that the chronic inflammation is a shared mechanism in the initiation and progression of multiple neurodegenerative diseases with diverse clinical manifestations such as Alzheimer's disease (AD) and Multiple sclerosis (MS). Restricted cell renewal and regenerative capacity make the neural tissues extremely vulnerable to the uncontrolled inflammatory process leading to irreversible tissue damage. AREAS COVERED: A predominant consequence of increased inflammatory signaling is the upregulation of the transcription factor, NF-κB with subsequent neuroprotective or deleterious effects depending on the strength of the signal and the type of NF-κB dimers activated. We discuss the interplay between neuroinflammation and neurodegeneration keeping in focus NF-κB signaling as the point of convergence of multiple pathways associated with the development of the neurodegenerative pathologies, AD and MS. EXPERT OPINION: Considerable interest exists in developing efficient NF-κB inhibitors for neurodegenerative diseases. The review includes an overview of natural compounds and rationally designed agents that inhibit NF-κB and mediate neuroprotection in AD and MS. The key chemical moieties of the natural and the synthetic compounds provide efficient leads for the development of effective small molecule inhibitors that selectively target NF-κB activation; this would result in the desired benefit to risk therapeutic effects.
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“Neuroinflammation is one of the major factors of AD and other disorders related to cholinergic transmission. It can be attenuated by reducing the expression of NF-κB-p65 via NLRP3 pathways.”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [142]
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“Thus targeting the transcription factor (NF-κβp65) could be the novel approach for the treatment of AD.”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [142]
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Metadata
- Authors
- Srinivasan, M., & Lahiri, D. K.
- Affiliations
- Indiana University (US)
- Indiana University School of Medicine (US)
- Venue
- Expert Opinion on Therapeutic Targets
- Publisher
- Informa UK Limited
- Published
- 2015-02-04
- Volume
- 19
- Issue
- 4
- Pages
- 471-487
- ISSN
- 1472-8222 (ISSN-L)
- 1744-7631
- PMC
- PMC5873291
- OpenAlex
- W1973257468
- Cited by
- 164
- References
- 108
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 11 · 2023: 13 · 2022: 16 · 2021: 21 · 2020: 19 · 2019: 16 · 2018: 19 · 2017: 10 · 2016: 10 · 2015: 6
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Expert Opinion on Therapeutic Targets (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- Author eBooks
- Funders
- National Institutes of Health (5r21ag042804-02)
- National Institute on Aging (R21-AG042804, 5R21AG042804, 1R21AG047)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- NF-κB signaling, Alzheimer's disease, multiple sclerosis, neuroinflammation, neurodegeneration, NF-κB inhibitors, neuroprotection, natural compounds, small molecule inhibitors, chronic inflammation
- MeSH terms
- Alzheimer Disease, Animals, Humans, Multiple Sclerosis, Drug Design, Signal Transduction, Up-Regulation, NF-kappa B, Neuroprotective Agents
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