Challenges associated with curcumin therapy in Alzheimer disease

Abstract

Curcumin, the phytochemical agent in the spice turmeric, which gives Indian curry its yellow colour, is also a traditional Indian medicine. It has been used for millennia as a wound-healing agent and for treating a variety of ailments. The antioxidant, anti-inflammatory, antiproliferative and other properties of curcumin have only recently gained the attention of modern pharmacology. The mechanism of action of curcumin is complex and multifaceted. In part, curcumin acts by activating various cytoprotective proteins that are components of the phase II response. Over the past decade, research with curcumin has increased significantly. In vitro and in vivo studies have demonstrated that curcumin could target pathways involved in the pathophysiology of Alzheimer disease (AD), such as the β-amyloid cascade, tau phosphorylation, neuroinflammation or oxidative stress. These findings suggest that curcumin might be a promising compound for the development of AD therapy. However, its insolubility in water and poor bioavailability have limited clinical trials and its therapeutic applications. To be effective as a drug therapy, curcumin must be combined with other drugs, or new delivery strategies need to be developed.

Biological and therapeutic activities, and anticancer properties of curcumin

“…Oxidative damage and inflammatory processes are known to be particularly high in the brains of Alzheimer patients, and as the aqueous extract of turmeric reduces and prevents oxidation, it may be used concurrently in long-term therapy (46)(47)(48)(49).…”

PE859, A Novel Curcumin Derivative, Inhibits Amyloid-β and Tau Aggregation, and Ameliorates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8

“…In the A␤ 1-42 ELISA kit, anti-A␤ antibodies clone no. BNT77, which detects A␤ [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] , and clone no. BC05, which detects Cterminus of A␤ , were used.…”

“…Accordingly, the incidence of AD is significantly greater in the US than in India, where curcumin is consumed on a daily basis [19]. However, curcumin is difficult to use as an AD drug because of its poor bioavailability [20]. In contrast with curcumin, PE859 exhibited higher inhibitory activity against the aggregation of both A␤ and tau in vitro, and higher absorption into the blood and penetration of the blood-brain barrier in vivo [16].…”

Effects of curcumin on hippocampal expression of NgR and axonal regeneration in Aβ-induced cognitive disorder rats

“…It is safe, with little to no toxicity, and possesses antitumor, antioxidant, anti-inflammatory, antiapoptosis, and lipid-reducing pharmacological effects (Motterlini et al, 2000;Ringman et al, 2005;Heneka and O'Banion, 2007). Curcumin has also been used in the prevention and treatment of Alzheimer's disease (AD) (Xiong et al, 2011;Belkacemi et al, 2011;Huang et al, 2012), but the mechanism remains elusive. Epidemiological studies have shown that India has the lowest incidence of AD in the world (Wang and Du, 2003;Perry and Howes, 2011).…”