Clinical development of curcumin in neurodegenerative disease

Abstract

Curcumin, a polyphenolic antioxidant derived from the turmeric root has undergone extensive preclinical development, showing remarkable efficacy in wound repair, cancer and inflammatory disorders. This review addresses the rationale for its use in neurodegenerative disease, particularly Alzheimer's disease. Curcumin is a pleiotropic molecule, which not only directly binds to and limits aggregation of the β-sheet conformations of amyloid characteristic of many neurodegenerative diseases but also restores homeostasis of the inflammatory system, boosts the heat shock system to enhance clearance of toxic aggregates, scavenges free radicals, chelates iron and induces anti-oxidant response elements. Although curcumin corrects dysregulation of multiple pathways, it may exert many effects via a few molecular targets. Pharmaceutical development of natural compounds like curcumin and synthetic derivatives have strong scientific rationale, but will require overcoming various hurdles including; high cost of trials, concern about profitability and misconceptions about drug specificity, stability, and bioavailability.

Keywords: Alzheimer’s disease; activator protein 1; amyloid; amyloid-binding; antioxidant; brain derived neurotrophic factor; c-jun N terminal kinase; heat shock proteins; misfolded proteins; neurodegeneraton; neuroinflammation; non-steroidal anti-inflammatory drugs; nuclear factor kappa B; polyphenolic antioxidants.

Figure 1. Curcumin is a pleiotropic molecule correcting dysregulation of pathways in Alzheimer’ models

Pleiotropic actions of curcumin that could exert neuroprotection, neural repair, remove misfolded proteins in multiple neurodegenerative diseases.