title: 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.
authors.affiliation: Greater Los Angeles Healthcare System, Veteran's Administration, Geriatric Research Education and Clinical Center, Los Angeles, USA.
authors.forename: Shuxin
authors.initials: S
authors.lastname: Hu
authors.forename: Panchanan
authors.initials: P
authors.lastname: Maiti
authors.forename: Qiulan
authors.initials: Q
authors.lastname: Ma
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zuo
authors.forename: Mychica R
authors.initials: MR
authors.lastname: Jones
authors.forename: Greg M
authors.initials: GM
authors.lastname: Cole
authors.forename: Sally A
authors.initials: SA
authors.lastname: Frautschy
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003474:Curcumin / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000473:pathology; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016875:tau Proteins; D003474:Curcumin
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