ABSTRACT
Alzheimer’s disease (AD) is the most common form of dementia in elderly people and the fth leading cause of death for people who are 65 years or older (Alz. Assoc. Facts and Figures 2011). Neuropathologically, depositions of amyloid beta (Aβ) plaques in the brain interstitial and phosphorylation of microtubule-associated protein tau (MAPT) within axons are the hallmarks of AD (Hardy and Selkoe 2002). Aβ peptide, which is the proteolytic cleaved product of the transmembrane amyloid precursor protein (APP), is released by enzymatic cleavage by several secretase enzymes. APP is rst cleaved by β-secretase (or BACE-1) to produce sAPPβ and a 99 amino acid fragment, which is further cleaved by γ-secretase to produce Aβ peptides (39-44 amino acids residue) (Sambamurti et al. 2002). Alternatively, APP can also be cleaved by another enzyme, α-secretase, to produce sAPPα and a 83 amino acid residue fragment (C83), which is further cleaved by γ-secretase to produce P3 fragment and precludes Aβ production (Lahiri et al. 2003; Marlow et al. 2003). Decreasing the levels of
11.1 Introduction .......................................................................................................................... 259 11.2 Role of Curcumin in Neurodegenerative Diseases ............................................................... 261
11.2.1 Inammation and AD ............................................................................................... 261 11.2.2 Role of Activated Glia .............................................................................................. 262 11.2.3 Role of Nuclear Factor Kappa Beta .......................................................................... 262 11.2.4 Role of Peroxisome Proliferator-Activated Receptor G ............................................ 263
11.3 Curcumin in APP Processing ............................................................................................... 263 11.4 Curcumin and Tauopathies ................................................................................................... 263 11.5 AD Is a Synaptic Failure: Curcumin’s Effect on Pre-and Postsynaptic Proteins ................264 11.6 Curcumin and Its Effect on the Levels of BDNF and NGF .................................................264 11.7 Curcumin: Bioavailability ....................................................................................................266 11.8 Conclusion and Future Directions ........................................................................................266 Abbreviations .................................................................................................................................266 Acknowledgments .......................................................................................................................... 267 References ...................................................................................................................................... 267
APP and the activities of BACE-1 and γ-secretase has already been identied as potential therapeutic strategies for the treatment of AD (Lahiri et al. 2007a; Imbimbo and Giardina 2011; Vassar and Kandalepas 2011). The schematic diagram in Figure 11.1 shows the major APP processing pathways.
