Research on Green Tea Extract - 1 of 2

Effect of a 4-Month Tea Intervention on Oxidative DNA   Damage among Heavy Smokers: Role of Glutathione S-Transferase Genotypes.

Cancer Epidemiol Biomarkers Prev. 2004 Feb;13(2):242-9.  

Hakim IA, Harris RB, Chow HH, Dean M, Brown S, Ali IU.

Mel and Enid Zuckerman Arizona College of Public Health, University of Arizona   and Arizona Cancer Center, Tucson, Arizona.

Glutathione S-transferase (GST), a member of the phase II group of xenobiotic   metabolizing enzymes, has been intensively studied at the levels of phenotype   and genotype. The GST micro 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null-allele   variant in which the entire gene is absent. The null genotype for both enzymes   has been associated with many different types of tumors. The aim of this study   was to determine the possible differences in increased oxidative stress susceptibility   to smoking within the GSTM1 and GSTT1 genotypes and the impact of high tea drinking   on this. We designed a Phase II randomized, controlled, three-arm tea intervention   trial to study the effect of high consumption (4 cups/day) of decaffeinated   green or black tea, or water on oxidative DNA damage, as measured by urinary   8-hydroxydeoxyguanosine (8-OHdG), among heavy smokers over a 4-month period   and to evaluate the roles of GSTM1 and GSTT1 genotypes as effect modifiers.   A total of 133 heavy smokers (100 females and 33 males) completed the intervention.   GSTM1 and GSTT1 genotype statuses were determined with a PCR-based approach.   Multiple linear regression models were used to estimate the main effects and   interaction effect of green and black tea consumption on creatinine-adjusted   urinary 8-OHdG, with or without adjustment for potential confounders. Finally,   we studied whether the effect of treatment varied by GSTM1 and GSTT1 status   of the individual. Although there were no differences in urinary 8-OHdG between   the groups at baseline, the between-group 8-OHdG levels at month 4 were statistically   significant for GSTM1-positive smokers (P = 0.05) and GSTT1-positive smokers   (P = 0.02). GSTM1-positive and GSTT1-positive smokers consuming green tea showed   a decrease in urinary 8-OHdG levels after 4 months. Assessment of urinary 8-OHdG   after adjustment for baseline measurements and other potential confounders revealed   significant effect for green tea consumption (P = 0.001). The change from baseline   was significant in both GSTM1-positive (t = -2.99; P = 0.006) and GSTT1-positive   (P = 0.004) green tea groups, but not in the GSTM1-negative (P = 0.07) or GSTT1-negative   (P = 0.909) green tea groups. Decaffeinated black tea consumption had no effect   on urinary 8-OHdG levels among heavy smokers. Our data show that consumption   of 4 cups of tea/day is a feasible and safe approach and is associated with   a significant decrease in urinary 8-OHdG among green tea consumers after 4 months   of consumption. This finding also suggests that green tea intervention may be   effective in the subgroup of smokers who are GSTM1 and/or GSTT1 positive.

PMID: 14973088 [PubMed - in process]

Comparative study of the growth-inhibitory and apoptosis-inducing activities   of black tea theaflavins and green tea catechin on murine myeloid leukemia cells.

Int J Mol Med. 2004 Mar;13(3):465-71.

Lung HL, Ip WK, Chen ZY, Mak NK, Leung KN.

Department of Biochemistry, The Chinese University of Hong Kong, Shatin, China.

Among the black tea polyphenols, theaflavins are generally considered to be   the more effective components for the inhibition of carcinogenesis. In this   study, we attempted to compare the growth-inhibitory and apoptosis-inducing   activities of the four black tea theaflavins (TF-1, TF-2A, TF-2B and TF-3) with   the major green tea catechin epigallocatechin-3-gallate (EGCG) on the murine   myeloid leukemia WEHI-3B JCS cells. All the four black tea theaflavins were   shown to exert potent anti-proliferative and cytotoxic effects on the leukemia   WEHI-3B JCS cells in a dose-dependent manner. The observed anti-proliferative   and cytotoxic effects were in the following order of potency: EGCG > TF-2B   > TF-3 > TF-2A > TF-1. In addition, all theaflavins were capable of   inducing apoptosis in the leukemia WEHI-3B JCS cells. Among the four theaflavins   tested, TF-2B and TF-3 were found to be slightly more potent in inducing apoptosis   of the WEHI-3B JCS cells than that of TF-2A and TF-1 but were comparable to   the major green tea epicatechin EGCG. More interestingly, both TF-2B and TF-3   were found to be much more effective than TF-1 and TF-2B in reducing both the   in vitro clonogenicity and in vivo tumorigenicity of the WEHI-3B JCS cells,   suggesting that these two black tea theaflavins might represent potential candidates   for the treatment of some forms of leukemia.

PMID: 14767581 [PubMed - in process]

EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading   to suppression of cell viability and induction of apoptosis.

Int J Oncol. 2004 Mar;24(3):703-10.

Mittal A, Pate MS, Wylie RC, Tollefsbol TO, Katiyar   SK.

Department of Dermatology, University of Alabama at Birmingham, Birmingham,   AL 35294, USA.

Telomerase is elevated in >90% of breast carcinomas and therefore has received   much attention as a target for breast cancer therapy and cancer diagnostic research.   Dietary components that are capable of inhibiting the growth of cancer cells   without affecting the growth of normal cells are receiving considerable attention   in developing novel cancer-preventive approaches. Studies have shown that (-)-epigallocatechin-3-gallate   (EGCG) from green tea imparts a growth inhibitory effect on cancer cells. Here,   we show that treatment of EGCG dose-dependently inhibited (20-100%) the reproductive   or colony forming potential, and also decreased cell viability at different   time points studied ( approximately 80% inhibition) in human breast carcinoma   MCF-7 cells but had no adverse effect on the growth of normal mammary cells.   Treatment of EGCG for 48 and 72 h markedly increased the percentage of apoptotic   cells (32-51%) in MCF-7 cells compared to that of non-EGCG treated cells (8-14%).   In order to identify the possible mechanism of decreased cell viability and   induction of apoptosis in breast carcinoma cells by EGCG, we found that treatment   of MCF-7 cells with EGCG dose-dependently inhibited telomerase activity (40-55%),   and also inhibited the mRNA expression (40-55%) of hTERT, a catalytic subunit   of telomerase. Additional studies demonstrated that EGCG also inhibited the   protein expression of hTERT, which indicated that inhibition of telomerase was   associated with down-regulation of hTERT. Together, our results indicate that   EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading   to the suppression of cell viability and induction of apoptosis, thus providing   the molecular basis for the development of EGCG as a novel chemopreventive and   pharmacologically safe agent against breast cancer.

PMID: 14767556 [PubMed - in process]

Effect of Green Tea Supplementation on Insulin Sensitivity in Sprague-Dawley   Rats.

J Agric Food Chem. 2004 Feb 11;52(3):643-648.

Wu LY, Juan CC, Ho LT, Hsu YP, Hwang LS.

Graduate Institute of Food Science and Technology, National Taiwan University,   Taipei, Taiwan 106; Department of Medical Research and Education, Taipei Veterans   General Hospital, Taipei, Taiwan, 112; and Institute of Physiology and Clinical   Medicine, School of Medicine, Yang-Ming University, Taipei, Taiwan 112.

Epidemiological observations and laboratory studies have shown that green tea   has a variety of health effects, including antitumor, antioxidative, and hypolipidemic   activities. The aim of this study was to examine whether it had an effect on   glucose tolerance and insulin sensitivity in Sprague-Dawley rats. In experiment   1 (in vivo study), rats were divided into two groups: a control group fed standard   chow and deionized distilled water and a "green tea" group fed the   same chow diet but with green tea instead of water (0.5 g of lyophilized green   tea powder dissolved in 100 mL of deionized distilled water). After 12 weeks   of green tea supplementation, the green tea group had lower fasting plasma levels   of glucose, insulin, triglyceride, and free fatty acid than the control rats.   Insulin-stimulated glucose uptake of, and insulin binding to, adipocytes were   significantly increased in the green tea group. In experiment 2 (in vitro study),   a tea polyphenol extract was used to determine its effect on insulin activity   in vitro. Green tea polyphenols (0.075%) significantly increased basal and insulin-stimulated   glucose uptake of adipocytes. Results demonstrated that green tea increases   insulin sensitivity in Sprague-Dawley rats and that green tea polyphenol is   one of the active components.

PMID: 14759162 [PubMed - as supplied by publisher]

Growth inhibition of prostate cancer cells by epigallocatechin gallate in the   presence of cu(2+).

J Agric Food Chem. 2004 Feb 11;52(3):462-6.

Yu HN, Yin JJ, Shen SR.

Department of Tea Sciences, Zhejiang University, Hangzhou 310029, Peoples Republic   of China, and Center for Food Safety and Applied Nutrition, U.S. Food and Drug   Administration, College Park, Maryland 20740.

Green tea is an effective chemopreventive agent to human prostate cancer adenoma   (PCA). Epigallocatechin gallate (EGCG) inhibited the growth of PCA cells and   induced apoptosis. Cu(2+) is a trace element necessary to our health. Many studies   proved that bioactivity of EGCG is altered in the presence of Cu(2+). We investigated   the effects of EGCG on PCA cells in the presence of Cu(2+). Also, we explored   potential mechanisms via measurement of the relative chemiluminescence of growth   medium for PCA cells. Chemiluminscence can be an indication of free radicals.   Our test results showed that the addition of EGCG and Cu(2+) to the growth medium   decreased the relative viability of androgen-sensitive and androgen-insensitive   human prostate cancer cells. However, the effects of EGCG on PCA cells depended   on (1) the relative concentrations of added EGCG and Cu(2+) and (2) their order   of addition. Our results indicated that few free radicals may be generated in   vitro. If so, free radicals generated intracellularly may be a major factor   behind apoptosis and growth inhibition observed in the PCA cells. Thus, EGCG   might exert its effects intracellularly.

PMID: 14759133 [PubMed - in process]

Inhibitory effect of epigallocatechin 3-O-gallate on vascular smooth muscle   cell hypertrophy induced by angiotensin II.

J Cardiovasc Pharmacol. 2004 Feb;43(2):200-8.

Zheng Y, Song HJ, Kim CH, Kim HS, Kim EG, Sachinidis   A, Ahn HY.

Department of Pharmacology, College of Medicine, Chungbuk National University,   Cheongju, South Korea.

Recent evidence indicates that epigallocatechin 3-O-gallate (EGCG), the major   catechin derived from green tea leaves, lowers the risk of cardiovascular diseases   such as atherosclerosis and hypertension. However, a precise mechanism for this   biologic function has not yet been clearly delineated. Angiotensin II (Ang II)   stimulates vascular smooth muscle cell (VSMC) hypertrophy, which is a critical   event in the development of atherosclerosis, hypertension, and angioplasty-induced   restenosis. In the present study, we show that EGCG inhibits Ang II-stimulated   VSMC hypertrophy, as determined by [3H]leucine incorporation into VSMC. Since   mitogen-activated protein kinase (MAPK) families are involved in cell growth,   we determined whether EGCG affects them. EGCG pretreatment did not exert any   significant changes in Ang II-stimulated activation of extracellular signal-regulated   kinase (ERK) and p38 MAPK. EGCG only inhibited Ang II-stimulated activation   of c-Jun N-terminal kinase (JNK). Moreover, EGCG suppressed Ang II-induced c-jun   mRNA expression. In contrast, EGC, a structural analogue of EGCG, did not inhibit   the JNK activity or c-jun mRNA expression. In addition, a specific JNK inhibitor,   SP600125, dose-dependently suppressed Ang II-stimulated VSMC hypertrophy. These   results suggest that the effect of EGCG on Ang II-induced VSMC hypertrophy is   due to specific inhibition of the JNK signaling pathway at both transcriptional   and posttranslational levels, which may underlie its beneficial effect on the   cardiovascular diseases.

PMID: 14716206 [PubMed - in process]

Green tea polyphenol (-)-epigallocatechin gallate attenuates the neuronal NADPH-d/nNOS   expression in the nodose ganglion of acute hypoxic rats.

Brain Res. 2004 Feb 27;999(1):73-80.

Wei IH, Wu YC, Wen CY, Shieh JY.

Department of Anatomy and Cell Biology, College of Medicine, National Taiwan   University, 1, Section 1, Jen-Ai Road, 100, Taipei, Taiwan

Recent studies have shown that (-)-epigallocatechin gallate (EGCG), one of   the green tea polyphenols, has a potent antioxidant property. Nitric oxide (NO)   plays an important role in the neuropathogenesis induced by brain ischemia/reperfusion   and hypoxia. This study aimed to explore the potential neuroprotective effect   of EGCG on the ganglionic neurons of the nodose ganglion (NG) in acute hypoxic   rats. Thus, the young adult rats were pretreated with EGCG (10, 25, or 50 mg/kg,   i.p.) 30 min before they were exposed to the altitude chamber at 10,000 m with   the partial pressure of oxygen set at the level of 0.27 atm (pO(2)=43 Torr)   for 4 h. All the animals examined were allowed to survive for 3, 7, and 14 successive   days, respectively, except for those animals sacrificed immediately following   hypoxic exposure. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d)   histochemistry and neuronal nitric oxide synthase (nNOS) immunohistochemistry   were carried out to detect the neuronal NADPH-d/nNOS expression in the NG. The   present results show a significant increase in the expression of NADPH-d/nNOS   reactivity in neurons of the NG at various time intervals following hypoxia.   However, the hypoxia-induced increase in NADPH-d/nNOS expression was significantly   depressed only in the hypoxic rats treated with high dosages of EGCG (25 or   50 mg/kg). These data suggest that EGCG may attenuate the oxidative stress following   acute hypoxia.

PMID: 14746923 [PubMed - in process]

Effects of green tea polyphenols on murine transplant-reactive T cell immunity.

Clin Immunol. 2004 Jan;110(1):100-8.

Bayer J, Gomer A, Demir Y, Amano H, Kish DD, Fairchild   R, Heeger PS.

The Transplantation Research Program, The Department of Immunology and The   Glickman Urologic Institute, The Cleveland Clinic Foundation, Cleveland, OH   44195, USA.

Green tea polyphenols (GrTP), the active ingredient of green tea, may have   immunosuppressive properties, but whether and how GrTP affect transplant-reactive   T cells is unknown. To address this, we tested the effects of GrTP on in vitro   and in vivo transplant-reactive T cell immunity. GrTP inhibited IFNgamma secretion   by cultured monoclonal T cells and by alloreactive T cells in mixed lymphocyte   reactions. Oral GrTP significantly prolonged minor antigen-disparate skin graft   survival and decreased the frequency of donor-reactive interferon gamma-producing   T cells in recipient secondary lymphoid organs compared to controls. In contrast   to other hypothesized actions, oral GrTP did not alter dendritic cell trafficking   to lymph nodes or affect metalloproteinase activity in the graft. This is the   first report of an immunosuppressive effect of GrTP on transplant-reactive T   cell immunity. The results suggest that oral intake of green tea could act as   an adjunctive therapy for prevention of transplant rejection in humans.

PMID: 14962801 [PubMed - in process]

Green tea inhibits human inducible nitric-oxide synthase expression by down-regulating   signal transducer and activator of transcription-1alpha activation.

Mol Pharmacol. 2004 Jan;65(1):111-20.

Tedeschi E, Menegazzi M, Yao Y, Suzuki H, Forstermann   U, Kleinert H.

Biochemistry Section, Department of Neuroscience and Vision, University of   Verona, Verona, Italy.

Green tea has been reported to show anti-inflammatory properties because of   its inhibitory effects on the expression of several pro-inflammatory genes.   Because the inducible nitricoxide synthase (iNOS) plays an important role in   chronic inflammatory diseases, we have focused our attention on the regulation   of iNOS expression by green tea in two different human epithelial cell lines,   alveolar A549/8 and colon DLD-1 cells. With the use of electrophoretic mobility   shift assays, we found a green tea-mediated down-regulation of the DNA binding   activity of the transcription factor signal transducer and activator of transcription-1alpha   (STAT-1alpha), but not of nuclear factor-kappaB. This down-regulation of the   STAT-1alpha DNA binding was shown to result from reduced tyrosine phosphorylation   of the STAT-1alpha protein and not from antioxidative effects of the green tea   extract. Green tea extract inhibited human iNOS expression in a concentration-dependent   manner, quantified in terms of iNOS mRNA, iNOS protein, and nitric oxide production   in both cell lines. This inhibitory effect of green tea resulted from transcriptional   inhibition as shown in reporter gene experiments. These data suggest that green   tea extracts may be promising at least as an auxiliary anti-inflammatory principle   in chronic inflammatory diseases.

PMID: 14722242 [PubMed - indexed for MEDLINE]

A nested case-control study of stomach cancer in relation to green tea consumption   in Japan.

Br J Cancer. 2004 Jan 12;90(1):135-8.

Hoshiyama Y, Kawaguchi T, Miura Y, Mizoue T, Tokui N,   Yatsuya H, Sakata K, Kondo T, Kikuchi S, Toyoshima H, Hayakawa N, Tamakoshi   A, Ohno Y, Yoshimura T; Japan Collaborative Cohort Study Group.

Department of Public Health, Showa University School of Medicine, 1-5-8 Hatanodai,   Shinagawa, Tokyo 142-8555, Japan. yhkiss@med.showa-u.ac.jp

To evaluate whether green tea consumption provides protection against stomach   cancer, the relative risks (RRs) were calculated in the Japan Collaborative   Study for Evaluation of Cancer Risk, sponsored by the Ministry of Health and   Welfare (JACC Study). The study was based on 157 incident cases and 285 controls   aged 40-79 years. Cox proportional hazards regression analysis was used to estimate   the RRs for stomach cancer. It was found that green tea consumption had no protective   effect against stomach cancer. After adjustment for age, smoking status, H.   pylori infection, history of peptic ulcer, and family history of stomach cancer   along with certain dietary elements, the risks associated with drinking one   or two, three or four, five to nine, and 10 or more cups of green tea per day,   relative to those of drinking less than one cup per day, were 1.3 (95% confidence   interval (CI): 0.6-2.8), 1.0 (95% CI: 0.5-1.9), 0.8 (95% CI: 0.4-1.6), and 1.2   (95% CI: 0.6-2.5), respectively (P for trend=0.899). We found no inverse association   between green tea consumption and the risk of stomach cancer.

PMID: 14710220 [PubMed - in process]

Lipid raft-associated catechin suppresses the FcepsilonRI expression by inhibiting   phosphorylation of the extracellular signal-regulated kinase1/2.

FEBS Lett. 2004 Jan 2;556(1-3):204-10.

Fujimura Y, Tachibana H, Yamada K.

Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu   University, 6-10-1 Hakozaki, Higashi-ku, 812-8581, Fukuoka, Japan.

The major green tea catechin, (-)-epigallocatechin-3-O-gallate   (EGCG), has a suppressive effect on the expression of the high-affinity IgE   receptor FcepsilonRI, which is key molecule in the IgE-mediated allergic reactions.   Here we show that EGCG binds to the cell surface and highly associates with   plasma membrane microdomains, lipid rafts, on the human basophilic KU812 cells.   The disruption of these lipid rafts caused a reduction of the amount of raft-associated   EGCG and the FcepsilonRI-suppressive effect of EGCG. We also found that EGCG   has an ability to inhibit the phosphorylation of the extracellular signal-regulated   kinase1/2 (ERK1/2) and that the ERK1/2 specific inhibitor also reduced FcepsilonRI   expression. Moreover, the inhibitory effect elicited by EGCG on ERK1/2 was prevented   by disruption of rafts. Thus, these results suggest that the interaction between   EGCG and the lipid rafts is important for EGCG's ability to downregulate FcepsilonRI   expression, and ERK1/2 may be involved in this suppression signal.

PMID: 14706851 [PubMed - in process]

Inhibitory effect of green tea catechins on cysteine   proteinases in Porphyromonas gingivalis.

Oral Microbiol Immunol. 2004 Apr;19(2):118-120.

Okamoto M, Sugimoto A, Leung KP, Nakayama K, Kamaguchi   A, Maeda N.

Department of Oral Bacteriology, Tsurumi University School of Dental Medicine,   Kanagawa, Japan, Itoen Ltd, Shizuoka, Japan, US Army Dental Research Detachment,   Great Lakes, IL, USA, Department of Microbiology, School of Dentistry, Nagasaki   University, Nagasaki, Japan, Department of Oral Microbiology, School of Dentistry,   Health Sciences University of Hokkaido, Hokkaido, Japan.

The purpose of this study was to examine the effects of catechins   and their derivatives on the activities of Arg-gingipain (Rgp) and Lys-gingipain   (Kgp) in Porphyromonas gingivalis. Catechin derivatives, which included (-)-epigallocatechin   gallate, (-)-epicatechin gallate, (-)-gallocatechin gallate, and (-)-catechin   gallate, significantly inhibited the Rgp activity. The 50% inhibitory concentrations   (IC50s) of these catechin derivatives for Rgp ranged from 3 to 5 microm. While   (-)-epigallocatechin and (-)-gallocatechin moderately inhibited Rgp activity   (IC50s, 20 microm), (-) -epicatechin, (+)-catechin, and gallic acid were not   effective, with IC50s greater than 300 microm. Further, some of the catechin   derivatives tested also inhibited the Kgp activity, though to a lesser extent   than inhibition of the Rgp activity. These findings suggest that green tea catechins   may have the potential to reduce periodontal breakdown resulting from the potent   proteinase activity of P. gingivalis.

PMID: 14871352 [PubMed - as supplied by publisher]

Green tea polyphenol epigallocatechin-3-gallate inhibits platelet-derived growth   factor-induced proliferation of human hepatic stellate cell line LI90.

J Hepatol. 2004 Jan;40(1):52-9.

Sakata R, Ueno T, Nakamura T, Sakamoto M, Torimura T,   Sata M.

Research Center for Innovative Cancer Therapy, Second Department of Medicine,   Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.   rsakata@med.kurume-u.ac.jp

BACKGROUND/AIMS: Green-tea polyphenols are known to have anti-fibrotic   properties of the skin and the artery. The proliferation of hepatic stellate   cells (HSC) is closely related to the progression of liver fibrosis in chronic   liver diseases. We investigated the inhibitory effect of epigallocatechin-3-gallate   (EGCG), the major potential inhibitory component of green-tea polyphenols, on   the proliferation of HSC. The aim of this study was to clarify the molecular   mechanisms of EGCG inhibition of HSC proliferation. METHODS: A cultured human   hepatic stellate cell line LI90 was used for this study. The cells were stimulated   by platelet-derived growth factor (PDGF)-BB in the presence or absence of EGCG.   Proliferation was determined by bromodeoxy-uridine incorporation. The mRNA expressions   of collagen alpha1(I) and (IV) were evaluated by a quantitative reverse transcription-polymerase   chain reaction. PDGF receptor tyrosine phosphorylation was detected using anti-phosphotyrosine   antibody. PDGF receptor radioligand binding assay was performed by [125I]-PDGF-BB.   RESULTS: EGCG inhibited the PDGF-BB-induced cell-proliferation and collagen   alpha1(I) and (IV) mRNA expressions. EGCG reduced the autophosphorylation of   the PDGF receptor. EGCG blocked PDGF-BB binding to its receptor in a non-competitive   manner. CONCLUSIONS: EGCG has an inhibitory effect on PDGF-induced proliferation   of HSC, and the blocking of PDGF-BB binding to its receptor may be the mechanism   behind this effect.

PMID: 14672614 [PubMed - in process]

Novel mechanisms and approaches in the study of neurodegeneration   and neuroprotection. a review.

Neurotox Res. 2003;5(6):375-83.

Kostrzewa RM, Segura-Aguilar J.

Department of Pharmacology, Quillen College of Medicine, East Tennessee State   University, Johnson City, TN 37614, USA. kostrzew@etsu.edu

Cellular mechanisms involved in neurodegeneration and neuroprotection   are continuing to be explored, and this paper focuses on some novel discoveries   that give further insight into these processes. Oligodendrocytes and activated   astroglia are likely generators of the pro-inflammatory cytokines, such as the   tumor necrosis factor family and interleukin family, and these glial support   cells express adhesion receptors (e.g., VCAM) and release intercellular adhesion   molecules (ICAM) that have a major role in neuronal apoptosis. Even brief exposure   to some substances, in ontogeny and sometimes in adulthood, can have lasting   effects on behaviors because of their prominent toxicity (e.g., NMDA receptor   antagonists) or because they sensitize receptors (e.g., dopamine D2 agonists),   possibly permanently, and thereby alter behavior for the lifespan. Cell cycle   genes which may be derived from microglia, are the most-recent entry into the   neuroprotection schema. Neuroprotection afforded by some common substances (e.g.,   melatonin) and uncommon substances [e.g., nicotine, green tea polyphenol (-)-epigallocatechin-3-gallate   (EGCG), trolox], ordinarily thought to be simple radical scavengers, now are   thought to invoke previously unsuspected cellular mechanisms in the process   of neuroprotection. Although Alzheimer's disease (AD) has features of a continuous   spectrum of neural and functional decline, in vivo PET imaging and and functional   magnetic resonance imaging, indicate that AD can be staged into an early phase   treatable by inhibitors of beta and gamma secretase; and a late phase which   may be more amenable to treatment by drugs that prevent or reverse tau phosphorylation.   Neural transplantation, thought to be the last hope for neurally injured patients   (e.g., Parkinsonians), may be displaced by non-neural tissue transplants (e.g.,   human umbilical cord blood; Sertoli cells) which seem to provide similar neurotrophic   support and improved behavior - without posing the major ethical dilemma of   removing tissue from aborted fetuses. The objective of this paper is to invite   added research into the newly discovered (or postulated) novel mechanisms; and   to stimulate discovery of additional mechanisms attending neurodegeneration   and neuroprotection.

PMID: 14715440 [PubMed - indexed for MEDLINE]