CONTINUATION OF ALZHEIMER'S ABSTRACTS

ALZHEIMER'S DISEASE --- CURCUMIN

Prog Neurobiol. 2007 Aug;82(6):348-60. Epub 2007 Jun 19.
Iron dysregulation in Alzheimer's disease: Multimodal brain permeable iron chelating drugs, possessing neuroprotective-neurorescue and amyloid precursor protein-processing regulatory activities as therapeutic agents.
Mandel S, Amit T, Bar-Am O, Youdim MB.
Eve Topf and USA NPF Centers of Excellence, Technion-Faculty of Medicine, Department of Pharmacology, Israel.

Considering the multi-etiological character of Alzheimer's disease (AD), the current pharmacological approaches using drugs oriented towards a single molecular target possess limited ability to modify the course of the disease and thus, offer a partial benefit to the patient. In line with this concept, novel strategies include the use of a cocktail of several drugs and/or the development of a single molecule, possessing two or more active neuroprotective-neurorescue moieties that simultaneously manipulate multiple targets involved in AD pathology. A consistent observation in AD is a dysregulation of metal ions (Fe(2+), Cu(2+) and Zn(2+)) homeostasis and consequential induction of oxidative stress, associated with beta-amyloid aggregation and neurite plaque formation. In particular, iron has been demonstrated to modulate the Alzheimer's amyloid precursor holo-protein expression by a pathway similar to that of ferritin L-and H-mRNA translation through iron-responsive elements in their 5'UTRs. This review will discuss two separate scenarios concerning multiple therapy targets in AD, sharing in common the implementation of iron chelation activity: (i) novel multimodal brain-permeable iron chelating drugs, possessing neuroprotective-neurorescue and amyloid precursor protein-processing regulatory activities; (ii) natural plant polyphenols (flavonoids), such as green tea epigallocatechin gallate (EGCG) and curcumin, reported to have access to the brain and to possess multifunctional activities, such as metal chelation-radical scavenging, anti-inflammation and neuroprotection.

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Adv Exp Med Biol. 2007;595:1-75.
Curcumin: the Indian solid gold.
Aggarwal BB, Sundaram C, Malani N, Ichikawa H.
Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. aggarwal@mdanderson.org

Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal "Spice for Life".

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Evid Based Complement Alternat Med. 2007 Jun;4(2):181-190. Epub 2007 Apr 23.
Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies.
Salvioli S, Sikora E, Cooper EL, Franceschi C.
Department of Experimental Pathology and Centro Interdipartimentale “L. Galvani”, University of Bologna, via S. Giacomo 12, 40126 Bologna, Italy, ER-GenTech laboratory, via Saragat 1, 44100 Ferrara, Italy, Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, 3 Pasteura St., 02-093 Warsaw, Poland, Laboratory of Comparative Neuroimmunology, Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles California 90095-1763 and I.N.R.C.A., Department of Gerontological Sciences, via Birarelli 8, 60121 Ancona, Italy.

Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.

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J Neurochem. 2007 Aug;102(4):1095-104. Epub 2007 Apr 30.
Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model.
Garcia-Alloza M, Borrelli LA, Rozkalne A, Hyman BT, Bacskai BJ.
Department of Neurology/Alzheimer's Disease Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.

Alzheimer's disease (AD) is characterized by senile plaques and neurodegeneration although the neurotoxic mechanisms have not been completely elucidated. It is clear that both oxidative stress and inflammation play an important role in the illness. The compound curcumin, with a broad spectrum of anti-oxidant, anti-inflammatory, and anti-fibrilogenic activities may represent a promising approach for preventing or treating AD. Curcumin is a small fluorescent compound that binds to amyloid deposits. In the present work we used in vivo multiphoton microscopy (MPM) to demonstrate that curcumin crosses the blood-brain barrier and labels senile plaques and cerebrovascular amyloid angiopathy (CAA) in APPswe/PS1dE9 mice. Moreover, systemic treatment of mice with curcumin for 7 days clears and reduces existing plaques, as monitored with longitudinal imaging, suggesting a potent disaggregation effect. Curcumin also led to a limited, but significant reversal of structural changes in dystrophic dendrites, including abnormal curvature and dystrophy size. Together, these data suggest that curcumin reverses existing amyloid pathology and associated neurotoxicity in a mouse model of AD. This approach could lead to more effective clinical therapies for the prevention of oxidative stress, inflammation and neurotoxicity associated with AD.

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