The Seed Extract of Cassia obtusifolia Offers Neuroprotection

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Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder and its pathological hallmarks include β-amyloid (Aβ) plaques, dystrophic neurites associated with plaques, and neurofibrillary tangles composed of hyperphosphorylated tau protein. The gradual degeneration of nerve cells and the resultant loss of specific synaptic connections in the brain is the key pathological change associated with the emergence and progression of AD, with the amygdala, hippocampus, parahippocampal, and other adjacent cortical regions being particularly susceptible to such degeneration.

The precise causative factors in neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s disease remain elusive, but mechanisms implicated comprise excitotoxicity, mitochondrial dysfunction, and in the case of AD, the amyloid beta peptide (Aβ). Current therapeutic strategies for such disorders are very limited; thus, traditional herbal medicines currently receive increased attention. The seeds of Cassia obtisufolia have long been used in traditional eastern medicine and more recently the ethanolic fraction of the seeds (COE) has been shown to attenuate memory impairments in mice. In this study, we set out to determine the effect of COE (range: 0.1 – 10 μg/ml) on calcium dysregulation and cell death models in mouse primary hippocampal cultures implicated in general neurodegenerative processes and in the pathogenesis of AD: excitotoxicity, mitochondrial dysfunction, and Aβ toxicity. It was found that treatment with COE attenuated secondary Ca2+ dysregulation induced by NMDA (700 μM), while a pre-application of COE also reduced NMDA-induced cell death. Furthermore, COE was neuroprotective against the mitochondrial toxin 3-NP (1 mM), while having no significant effect on cell death induced by incubation with naturally-secreted oligomers of Aβ (8.2 pg/ml). Collectively, these results are important for the therapeutic use of COE in the treatment of neurodegenerative disorders. http://www.jstage.jst.go.jp/article/jphs/107/4/380/_pdf

Science builds for L-carnitine and muscle ageing

Supplementation with L-carnitine may restore natural losses of the nutrient that occur naturally with age, according to a new study with rats. ...http://www.nutraingredients.com

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Zinc and copper ions induce the aggregation of Αβ peptides

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Alzheimer's disease (AD) is a neurodegenerative disease characterized by deposits of extracellular amyloid plaques and intracellular neurofibrillary tangles in the brain. The principal components of the plaques are fibrils formed of 40–42 residues long amyloid β-peptides (Αβ) derived from cleavage of amyloid precursor protein (APP) by β- and γ-secretases. Αβ aggregation is an established pathogenic mechanism of AD and therefore factors influencing the Αβ aggregation are of high interest. Aggregation of Αβ peptides is primarily affected by a variety of genetic and dietary factors leading to increased concentrations of Αβ peptides or to the excessive formation of Αβ peptides with increased tendency for aggregation i and copper ions may induce the aggregation of Αβ peptides and these ligands may act as seeding factors in the formation of amyloid plaques. Cu2+ and Zn2+ form complexes with Abeta peptides in vitro; however, the published metal-binding affinities of Abeta vary in an enormously large range. Authors studied the interactions of Cu2+ and Zn2+ with monomeric Abeta(40) under different conditions using intrinsic Abeta fluorescence and metal-selective fluorescent dyes. We showed that Cu(2+) forms a stable and soluble 1 : 1 complex with Abeta(40), however, buffer compounds act as competitive copper-binding ligands and affect the apparent K(D). Buffer-independent conditional K(D) for Cu(II)-Abeta(40) complex at pH 7.4 is equal to 0.035 micromol/L. Interaction of Abeta(40) with Zn2+ is more complicated as partial aggregation of the peptide occurs during zinc titration experiment and in the same time period (within 30 min) the initial Zn-Abeta(40) complex (K(D) = 60 micromol/L) undergoes a transition to a more tight complex with K(D) approximately 2 micromol/L. Competition of Abeta(40) with ion-selective fluorescent dyes Phen Green and Zincon showed that the K(D) values determined from intrinsic fluorescence of Abeta correspond to the binding of the first Cu2+ and Zn2+ ions to the peptide with the highest affinity. Interaction of both Zn2+ and Cu2+ ions with Abeta peptides may occur in brain areas affected by Alzheimer's disease and Zn2+-induced transition in the peptide structure might contribute to amyloid plaque formation. http://www3.interscience.wiley.com/cgi-bin

Green tea extract may lower blood pressure: study

Daily supplements of extracts from green tea (Camellia sinensis) may reduce blood pressure, cholesterol and markers of oxidative stress, and all within three weeks, says a new study. ...http://www.nutraingredients.com

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NP12 improves cognitive performance and reduces amyloid deposits

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Around 26 million people are affected by Alzheimer's disease worldwide, of which more than the half is entitled to seven major pharmaceutical markets (USA, Japan, Germany, UK, France, Italy and Spain). It is calculated that the number of AD sufferers worldwide will triple by the year 2050. The increase of the prevalence is a result of the progressive rise in life expectancy, the improvement in health care and diagnosis techniques.

Noscira, a company of Zeltia group devoted to the research and development of innovative drugs for the treatment of diseases of the nervous system, has received the approval of the Austrian health authorities and the Ethics Committee for the initiation of the first Phase II study with NP-12 for the treatment of Alzheimer's disease. NP-12, the first compound of Noscira's product pipeline, is an innovative drug of a new family of compounds. NP12 acts on the two main cellular processes that cause Alzheimer's disease, tau hyperphosphorylation and β-amyloid aggregation. Both in Alzheimer's disease and other neurodegenerative diseases, NP-12 may have a modifier and clinically relevant effect.

In Phase II clinical trials, NP12 will be administered to patients with Alzheimer's disease. Noscira is the only company in the world to have reached the clinical development stage with a compound for Alzheimer's disease, designed to inhibit the GSK3 enzyme. "This milestone reached by Noscira shows our progress in the search for new treatments, not only against cancer, through PharmaMar research activities, but also against other socially relevant diseases such as Alzheimer's disease" said Jose Maria Fernandez Sousa-Faro, President of Zeltia Group.

In words of Teodoro del Ser, Director of Clinical Development at Noscira, "We are pleased with the outcome of our work and with the efforts made at Noscira and we are confident that Phase II clinical trials results of NP12 will support our clinical expectations"

In animal models of Alzheimer's disease, it was demonstrated that NP12 improves cognitive performance and reduces amyloid deposits, hyperphosphorylation and tau aggregation, neuroinflammation and, most importantly, neuron loss, the ultimate cause of the clinical profile of progressive and widespread deterioration. Consistency of these findings supports the expectation that the compound may have a modifying effect of Alzheimer's disease when administered to patients. http://www.medicalnewstoday.com

Suck it and see: has the probiotic straw arrived?

The probiotic straw is a concept that has been a long time coming but one which may be about to move from its current niche status into the mainstream, according to Swedish probiotics supplier, BioGaia. ...http://www.nutraingredients.com

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2008

Amyloid beta clearance, transport and degradation

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Currently, the 'amyloid hypothesis' is the most widely accepted explanation for the pathogenesis of Alzheimer's disease (AD). According to this hypothesis, altered metabolism of the amyloid-beta (Abeta) peptide is central to the pathological cascade involved in the pathogenesis of AD. Although Abeta is produced by almost every cell in the body, a physiological function for the peptide has not been determined, and the pathways by which Abeta leads to cognitive dysfunction and cell death are unclear. Numerous therapeutic approaches that target the production, toxicity and removal of Abeta are being developed worldwide. Although therapeutic treatment for AD may be imminent, the value and effectiveness of such treatment are largely dependent on early diagnosis of the disease. This review summarizes current knowledge of Abeta clearance, transport and degradation, and evaluates the use of such information in the development of diagnostic tools. The conflicting results of plasma Abeta ELISAs are discussed, as are the more promising results of Abeta imaging by positron emission tomography. Current knowledge of Abeta-binding proteins and Abeta-degrading enzymes is analysed in the context of a potential therapy for AD. Transport across the blood-brain barrier by the receptor for advanced glycation end products and efflux via the multi-ligand lipoprotein receptor LRP-1 is also reviewed. Enhancing clearance and degradation of Abeta remains an attractive therapeutic strategy, and improved understanding of Abeta clearance may lead to advances in diagnostics and interventions designed to prevent or delay the onset of AD. Mol Psychiatry. 2008 Sep 16

Raw broccoli best for anti-cancer potential

Consuming cooked or processed broccoli may result in less of the potential anti-cancer compounds being available for absorption, suggests a new study from TNO Quality of Life. ...http://www.nutraingredients.com

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Aggregates of Amyloid beta induce neuronal cell cycle

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Neurons subject to degeneration in Alzheimer's disease (AD) exhibit evidence of re-entry into a mitotic cell cycle even before the development of substantial AD brain pathology. In efforts to identify the initiating factors underlying these cell cycle events , authors have characterized the appearance of the neuronal cell cycle events in the genomic-based transgenic mouse model of AD. Notably, the genomic-based transgenic mice exhibit neuronal cell cycle events in a reproducible temporal and spatial pattern that recapitulates the neuronal vulnerability seen in human AD. Neuronal cell cycle events first appear at 6 months in the frontal cortex layers II/III. This is 6-8 months before detectable amyloid beta (Abeta) deposition, suggesting that specific amyloid precursor protein (APP) processing products are responsible for the induction of neuronal cell cycle events. Furthermore, a reduction in the levels of Abeta dramatically delays the appearance of neuronal cell cycle events. More significantly, elimination of beta-secretase activity blocks the appearance of cell cycle events, providing direct genetic evidence that the amyloidogenic processing of APP is required for the induction of cell cycle events. Finally, in vitro preparations of oligomeric, but not monomeric, Abeta induce DNA synthesis in dissociated cortical neurons, and this response is blocked by antioligomer specific antibodies. Together, our data suggest that low molecular weight aggregates of Abeta induce neuronal cell cycle re-entry in mouse models of Alzheimer's disease. http://www.medicalnewstoday.com

Bilberry extract may ease the damages of stress: study

Extracts from bilberry may reduce stress-induced damage in the liver, according to a new study with mice. ...http://www.nutraingredients.com

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The development of AD therapeutics

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The past 25 years have seen an explosion of scientific investigations into the basic neurobiology of Alzheimer's disease (AD). At the same time, the gap between bench and bedside remains as vast as ever. Recent progress, however, has resulted in the development of novel, and in some cases, unconventional approaches for effective treatment. New therapies are currently undergoing preclinical investigation or are in clinical trial phase.

"The scientific community in general and the pharmaceutical industry in particular have invested heavily in just a few areas of AD therapeutics. The result is quite clear: symptomatic drugs are the best that can be offered to patients with this devastating disease," commented Dr. Chohan, Neuroimmunology Lab, Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities. "Despite the seemingly desperate state of affairs, we now see a steady influx of novel, unconventional therapeutic approaches."

Bringing together 14 contributions from worldwide experts, Dr. Chohan has assembled a two-part Special Issue. The first part concentrates mainly on preclinical studies and novel agents that are still in the experimental phase, while the second describes current clinical studies and some of the major issues involved.

The issue opens with a focus on immunotherapy. Einar Sigurdsson proposes active immunization against tau, while Michal Novak and his group elaborate on passive tau immunization. This is followed by an update on glycogen synthase kinase-3 (GSK-3) inhibitors by Daniel Perez and Anna Martinez, who lead a major AD clinical trial with a GSK-3 inhibitor. Although amyloid immunotherapy has been a particular focus of almost all large pharmaceutical efforts, there has been limited progress in that area. Beka Solomon proposes a completely novel approach based on phage-display technology which holds promise in amyloid-based vaccine development.

While there is growing literature on the involvement of oxidative stress in AD pathogenesis, clinical data have not shown substantial benefit from antioxidant agents. Two papers by Silvia Mandel and colleagues and Ashley Bush focus on a yet another novel approach: the role of metals and drugs based on the Metal Hypothesis. Kiminobu Sugaya and colleagues then discuss the promises and realities of cell replacement in the future of AD therapeutics. Finally, Antonio Cattaneo and colleagues discuss the potential of Nerve Growth Factor as a therapy for AD.

The development of AD therapeutics has been plagued with many failed and equivocal clinical trial outcomes. The second part of the special issue begins with a perspective from Saad Shafqat discussing the plight of dementia care in a developing country. This is followed by a series of stimulating analyses of current AD clinical trials both in the US and in Europe. First, Bruno Vellas and colleagues share their experience in the development of disease-modifying agents. Next, Robert Becker and colleagues and Cynthia Carlsson present an autopsy-style evaluation of failed AD clinical trials and make several important recommendations. Khalid Iqbal and colleagues wrap up the issue by discussing the multifactorial and heterogeneous nature of AD and the importance of patient stratification in the design of future clinical studies. http://www.medicalnewstoday.com (a special issue of the Journal of Alzheimer's Disease)

Lutein and zeaxanthin can benefit colon cancer, say researchers

Korean researchers have found alga-extracted carotenoids such as lutein and zeaxanthin can reduce colon cancer growths. ...http://www.nutraingredients.com

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Aβ Oligomers Induce Neuronal Cell Cycle Events in Alzheimer's

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Amyloid plaques are the defining characteristic of Alzheimer's disease (AD), but several studies suggest that soluble amyloid protein is more damaging to neurons. In fact, many signs of neurodegeneration occur before amyloid plaques appear. One such sign is neuronal re-entry into the cell cycle, which occurs in several neurodegenerative diseases. In humans with mild cognitive impairment, DNA replication and expression of cell cycle proteins (e.g., cyclins) appear in brain regions that undergo neurodegeneration in AD. Using transgenic mouse models of AD, Varvel et al. found that cyclins were expressed in frontal cortex many months before plaques appeared, and they were expressed even in mice that never develop plaques. Cyclin expression was prevented by blocking the abnormal processing of amyloid precursor protein that produces amyloid β. Furthermore, amyloid oligomers triggered DNA replication and cyclin expression in primary cortical neurons in vitro, indicating that this early characteristic of degeneration is triggered by soluble amyloid. http://www.medicalnewstoday.com

EFSA says yes to calcium

The latest batch of European Food Safety Authority (EFSA) opinions has surfaced with the assessor giving the thumbs up to three claims revolving around calcium, vitamin D and bone health. ...http://www.nutraingredients.com

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Statin therapy provides benefit in individuals with Alzheimer's

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Alzheimer's disease (AD) is the leading cause of dementia in the elderly, afflicting an estimated 4.5 million people in the U.S. Nymox Pharmaceutical Corporation holds U.S. and global patent rights for the use of statin drugs for the prevention and treatment of AD, including for patients at risk for AD because of vascular-related risk factors or disease. An important new study has found that ongoing statin drug use was associated with a 67% reduction in the risk of AD. The authors concluded that the "data suggest that statins produce a significant reduction in the risk of AD."

In the study, 2,233 people aged 70 years or older from six U.S. centers were followed for 4 years with annual assessments of cognitive changes. Subjects with suspected cognitive decline were referred for an in-depth evaluation for dementia and AD diagnosis. The study also tracked the use of statin and other cholesterol-lowering agents. Subjects who were taking statin drugs were found to have a statistically significant 67% reduction in the risk of AD.

The study authors also reviewed the other published studies assessing the effect of statin use on later risk of AD in the elderly and noted that 13 out of 15 of these studies had reported reduced risk for AD associated with cholesterol-lowering therapy. They concluded: "Overall, the evidence, with limited exceptions, suggests that statin therapy provides some level of benefit in treating individuals with AD, and prior statin use may reduce the risk of AD later in life."

Statins are widely used cholesterol-lowering drugs with a well-established track record of safety. They have an estimated global market over $25 billion and represent a potential new way of treating or preventing AD. Statin drug use has been shown to be associated with a lower risk of neuropathological changes in the brain of AD.

This press release contains certain "forward-looking statements" as defined in the United States Private Securities Litigation Reform Act of 1995 that involve a number of risks and uncertainties. There can be no assurance that such statements will prove to be accurate and the actual results and future events could differ materially from management's current expectations. The conduct of clinical trials and the development of drug products involve substantial risks and uncertainties and actual results may differ materially from expectations. Promising early results do not ensure that later stage or larger scale clinical trials will be successful or will proceed as expected. Such factors are detailed from time to time in Nymox's filings with the United States Securities and Exchange Commission and other regulatory authorities. http://www.medicalnewstoday.com

Tart cherries can reduce ‘belly fat’: rat study

Tart cherries, a relatively new entrant to the superfruit category, have been shown to benefit heart health as well as body weight, in a study on obese rats.

...http://www.nutraingredients.com

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