alzheimers disease

Mitochondrial oxidant signalling in Alzheimer's disease.: J Alzheimers Dis. 2007 May;11(2):175-81 Authors: Viña J, Lloret A, Vallés SL, Borrás C, Badía MC, Pallardó FV, Sastre J, Alonso MD

The role of free radicals in Alzheimer disease pathophysiology has been appreciated for a long time. Originally, radicals were considered as causative of oxidative damage. More recently their role as signalling molecules in this, as well as in other fields of free radical biology, has been underscored. Mitochondria are both generators and targets of radical damage in aging. In this paper we review evidence that radicals generated in mitochondria in the presence of Abeta are signals that trigger both the mitochondrial and the extra-mitochondrial pathways of apoptosis. There are gender specific differences in mitochondrial Abeta toxicity: mitochondria from young (but not from old) females appear to be protected. 17-beta Estradiol or phytoestrogens like genistein prevent the formation of oxidants by mitochondria and protect against mitochondrial Abeta toxicity. Experiments reported here indicate that phytoestrogens might have a role in the prevention of Alzheimer's disease.

Neuroprotective effects of green and black teas and their catechin gallate esters against beta-amyloid-induced toxicity.: Eur J Neurosci. 2006 Jan;23(1):55-64 Authors: Bastianetto S, Yao ZX, Papadopoulos V, Quirion R

Teas represent a large family of plants containing high amounts of polyphenols that may confer health benefits in various diseases. Recently, it has been hypothesized that tea consumption may also reduce the risk of age-related neurodegenerative pathologies. Considering the deleterious role of beta-amyloid (Abeta) in the aetiology of Alzheimer's disease (AD), we investigated green and black tea extracts and flavan-3-ols (present as monomers and dimers in green and black forms, respectively) against toxicity induced by Abeta-derived peptides using primary cultures of rat hippocampal cells as model. Both green and black tea extracts (5-25 microg/mL) displayed neuroprotective action against Abeta toxicity. These effects were shared by gallic acid (1-20 microm), epicatechin gallate (ECG; 1-20 microM) and epigallocatechin gallate (EGCG; 1-10 microM), the former being the most potent flavan-3-ol. In contrast, epicatechin and epigallocatechin were ineffective in the same range of concentrations. Moreover, only tea flavan-3-ol gallate esters (i.e. ECG, EGCG) and gallic acid inhibited apoptotic events induced by Abeta(25-35). Interestingly, EGCG and gallic acid inhibited Abeta aggregation and/or the formation of Abeta-derived diffusible neurotoxin ligands. Taken together, these results indicate that the catechin gallates (through the galloyl moiety) contribute to the neuroprotective effects of both green and black teas. Moreover, the protective effect of EGCG is likely to be associated, at least in part, with its inhibitory action on Abeta fibrils/oligomers formation. These data also support the hypothesis that not only green but also black teas may reduce age-related neurodegenerative diseases, such as AD.

Inhibitory effect of green tea extract on beta-amyloid-induced PC12 cell death by inhibition of the activation of NF-kappaB and ERK/p38 MAP kinase pathway through antioxidant mechanisms.: Brain Res Mol Brain Res. 2005 Oct 31;140(1-2):45-54 Authors: Lee SY, Lee JW, Lee H, Yoo HS, Yun YP, Oh KW, Ha TY, Hong JT

Beta-amyloid peptide (Abeta) is considered responsible for the pathogenesis of Alzheimer's disease (AD). Several lines of evidence support that Abeta-induced cytotoxicity is mediated through the generation of reactive oxygen species (ROS). Thus, agents that scavenge ROS level may usefully impede the development or progress of AD. Green tea extract has been known to have such antioxidant properties. Our previous studies demonstrate that green tea extract protected ischemia/reperfusion-induced brain cell death by scavenging oxidative damages of macromolecules. In this study, we investigated the effects of green tea extract on Abeta-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. PC12 cells treated with Abeta25-35 (10-50 microM) showed intracellular ROS elevation, the formation of 8-oxodG (an oxidized form of DNA), and underwent apoptotic cell death in a dose-dependent manner. Abeta(25-35) treatment upregulated pro-apoptotic p53 at the gene level, and Bax and caspase-3 at the protein level, but downregulated anti-apoptotic Bcl-2 protein. Interestingly, co-treated green tea extract (10-50 microg/ml) dose-dependently attenuated Abeta(25-35) (50 microM)-induced cell death, intracellular ROS levels, and 8-oxodG formation, in addition to p53, Bax, and caspase-3 expression, but upregulated Bcl-2. Furthermore, green tea extract prevented the Abeta(25-35)-induced activations of the NF-kappaB and ERK and p38 MAP kinase pathways. Our study suggests that green tea extract may usefully prevent or retard the development and progression of AD.

A potential role of the curry spice curcumin in Alzheimer's disease.: Curr Alzheimer Res. 2005 Apr;2(2):131-6 Authors: Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL

There is substantial in-vitro data indicating that curcumin has antioxidant, anti-inflammatory, and anti-amyloid activity. In addition, studies in animal models of Alzheimer's disease (AD) indicate a direct effect of curcumin in decreasing the amyloid pathology of AD. As the widespread use of curcumin as a food additive and relatively small short-term studies in humans suggest safety, curcumin is a promising agent in the treatment and/or prevention of AD. Nonetheless, important information regarding curcumin bioavailability, safety and tolerability, particularly in an elderly population is lacking. We are therefore performing a study of curcumin in patients with AD to gather this information in addition to data on the effect of curcumin on biomarkers of AD pathology.

Novel neuroprotective effects of the aqueous extracts from Verbena officinalis Linn.: Neuropharmacology. 2006 Jan 4; Authors: Lai SW, Yu MS, Yuen WH, Chang RC

Verbena officinialis Linn. (Verbenaceae) is a perennial plant which has been used as herbal medicine or health supplement in both Western and Eastern countries for centuries. It has been used to treat acute dysentery, enteritis, amenorrhea and depression. In view of its wide array of biological effects, we hypothesized that V. officinalis can exert cytoprotective effects on cells of the central nervous system. Pre-treatment of aqueous extracts of V. officinalis significantly attenuated the toxicity of beta-amyloid (Abeta) peptide and reducing agent dithiothreitol in primary cultures of cortical neurons. As extracellular accumulation of Abeta peptide is an important cytotoxic factor involved in Alzheimer's disease (AD), we have further explored its neuroprotective effect against Abeta. Treatment of V. officinalis attenuated Abeta-triggered DEVD- and VDVAD-cleavage activities in a dose-dependent manner. Further studies elucidated that phosphorylation of both interferon-inducing protein kinase (PKR) and c-Jun N-terminal kinase (JNK) was attenuated in Abeta-treated neurons. Taken together, we have proved our hypothesis by showing the novel neuroprotective effects of V. officinalis. As V. officinalis has long been used for many years to be a folk medicine, our study may provide a lead for its potential to be a neuroprotective agent against neuronal loss in AD.

Ginkgo biloba-an appraisal.: Kathmandu Univ Med J (KUMJ). 2004 Jul-Sep;2(3):225-9 Authors: Dubey AK, Shankar PR, Upadhyaya D, Deshpande VY

Ginkgo biloba has been used in traditional Chinese medicine for about 5000 years. A standardized preparation, EGb 761 has been recently prepared. The pharmacologically active constituents, flavonol glycosides and the terpene lactones are standardized. The terpene lactones comprise of ginkgolides A, B, C and bilobalides. The extract scavenges excess free radicals and pretreatment with EGb 761 reduces damage by free radicals in patients undergoing coronary bypass surgery. The action of platelet activating factor is antagonized and platelet aggregation is reduced. Blood flow is increased. Release of prostacyclines and nitric oxide was shown to be stimulated. Ginkgo biloba has been found to be useful in the treatment of Alzheimers disease and cognitive impairment. EGB 761 has shown beneficial effect in aging and mild cognitive impairment. Bilobalide has been shown to be protective against glutamate-induced excitotoxic neuronal death. Early studies indicate a potential role in age-related macular degeneration and some types of glaucoma. Anticancer action is related to antioxidant, anti-angiogenic and gene regulatory actions. Ginkgo biloba has shown overall improvement in about 65% of patients with cerebral impairment and a similar percentage suffering from peripheral vascular diseases. A recent study suggested that phytoestrogens in Ginkgo biloba may have a role as alternative hormone replacement therapy. Recent trials have not shown a beneficial effect of Ginkgo biloba in tinnitus and acute mountain sickness. Ginkgo biloba increased the bioavailability of diltiazem. The extract has been shown to protect against doxorubicin-induced cardiotoxicity and gentamicin-induced nephrotoxicity in animals. Ginkgo biloba inhibits microsomal enzymes and has a potential for drug interactions. Further studies to establish the efficacy of Ginkgo biloba are required.

Multiplicity of garlic health effects and Alzheimer's disease.: J Nutr Health Aging. 2005;9(6):421-32 Authors: Chauhan NB

The epidemiological, clinical and laboratory data have shown that garlic contains many biologically active compounds which are beneficial to human health in general. Among all, one garlic-preparation called aged garlic extract, is proven to be safer. Although additional studies are warranted in humans, compelling evidence supports the health effects attributed to aged garlic extract and its implications in preventing or reducing the risk of cardiovascular ailments, stroke and cancer. Recently, the beneficial effects of garlic and its constituents on neuronal physiology and brain functions are beginning to emerge. However, this field is still in infancy and not yet fully explored. This review encompasses multiple health effects of garlic and its constituents with reference to neuroprotection. Possible potential of dietary garlic as an alternative herbal pharmacotherapy for Alzheimer's disease is discussed.