Significance of NF-kappaB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer's disease and multiple sclerosis.

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Srinivasan M, Lahiri DK

Significance of NF-kappaB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer's disease and multiple sclerosis.

Expert Opin Ther Targets. 2015 Apr;19(4):471-87. doi: 10.1517/14728222.2014.989834. Epub 2015 Feb 4.

PubMed ID

25652642 [ View in PubMed

]

Abstract

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-kappaB with subsequent neuroprotective or deleterious effects depending on the strength of the signal and the type of NF-kappaB dimers activated. We discuss the interplay between neuroinflammation and neurodegeneration keeping in focus NF-kappaB 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-kappaB inhibitors for neurodegenerative diseases. The review includes an overview of natural compounds and rationally designed agents that inhibit NF-kappaB 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-kappaB activation; this would result in the desired benefit to risk therapeutic effects.

DrugBank Data that Cites this Article

Drugs

Donepezil

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Donepezil	Nuclear factor NF-kappa-B (Protein Group)	Protein group	Humans	Unknown	Inhibitor	Details