title: Significance of NF-κB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer's disease and multiple sclerosis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Indiana University School of Dentistry, Oral Pathology, Radiology and Medicine , Indianapolis, IN , USA +1 317 278 9686 ; +1 317 278 3018 ; mysriniv@iupui.edu.
authors: Mythily
authors: M
authors: Srinivasan
authors: Debomoy K
authors: DK
authors: Lahiri
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D015195:Drug Design; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents
keywords: Alzheimer’s disease; NF-κB; amyloid; disease modifying agents; drug target; multiple sclerosis; natural compounds; neurodegeneration; neuroinflammation; polyphenols; promoter; terpenoids; therapeutic target/mechanism
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