Proteasome inhibitor bortezomib inhibits T cell-dependent inflammatory responses - a new hope for autoimmune and inflammatory diseases?

In continuation of my update on Bortezomib, I found this info interesting to share with..

Japanese scientists lead by Dr. Koichi Yanaba, of Department of Dermatology at Nagasaki University Graduate School of Biomedical Sciences used mice to show that bortezomib, currently used to treat cancers that affect white blood cells, induces cell death only in harmful (active and proliferating) T cells, leaving the rest unharmed. If the results prove true in humans, it offers hope that this drugs or others similar to it might be used to treat inflammatory diseases without the side effects of current drugs that affect all T cells equally.

To make this discovery, scientists used two groups of mice the first treated with bortezomib and the second with saline. Researchers induced contact hypersensitivity reaction with oxazolone, a chemical allergen used for immunological experiments and found that bortezomib significantly inhibited the contact hypersensitivity responses. Results strongly suggest that bortezomib treatment enhanced T cell death by inhibiting NF-kappa B activation, which plays a key role in regulating the immune response to infection. This in turn led to the suppression of inflammatory responses in immune cells by reducing interferon-gamma production.

"We believe that this new-type remedy for autoimmune and inflammatory disease could successfully treat them in the near future", claims Dr. Koichi Yanaba...

As per the claim by the researchers, bortezomib potently inhibited CHS responses. The attenuation of CHS responses was associated with decreased inflammatory cell infiltration in the challenged skin. Specifically, bortezomib-treated mice showed significantly decreased numbers of CD4⁺ and CD8⁺ T cells in the challenged skin and draining lymph nodes. Cytoplasmic IFN- production by CD4⁺ and CD8⁺ T cells in the draining lymph nodes was decreased substantially by bortezomib treatment. Notably, bortezomib enhanced T cell apoptosis by inhibiting NF-B activation during CHS responses. Thus, bortezomib treatment is likely to induce T cell death, thereby suppressing CHS responses by reducing IFN- production. These findings suggest that bortezomib treatment could be a promising strategy for treating autoimmune and inflammatory disease.

Ref :http://www.jleukbio.org/cgi/content/abstract/88/1/117

How honey kills bacteria..........

We know that, honey has antibiotic activity and has been used specially in burn injuries. Now researchers lead by Dr.Sebastian A.J. Zaat, of Department of Medical Microbiology at the Academic Medical Center in Amsterdam, have come up with an explanation for this antibiotic activity of honey. This first explanation to explain how honey kills bacteria. Specifically, the research shows that bees make a protein that they add to the honey, called defensin-1, which could one day be used to treat burns and skin infections and to develop new drugs that could combat antibiotic-resistant infections.

"We have completely elucidated the molecular basis of the antibacterial activity of a single medical-grade honey, which contributes to the applicability of honey in medicine," said Dr. Sebastian A.J. Zaat...

To make the discovery, Dr. Zaat and colleagues investigated the antibacterial activity of medical-grade honey in test tubes against a panel of antibiotic-resistant, disease-causing bacteria. They developed a method to selectively neutralize the known antibacterial factors in honey and determine their individual antibacterial contributions. Ultimately, researchers isolated the defensin-1 protein, which is part of the honey bee immune system and is added by bees to honey. All bacteria tested, including Bacillus subtilis, methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase producing Escherichia coli, ciprofloxacin-resistant Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus faecium, were killed by 10–20% (v/v) honey, whereas 40% (v/v) of a honey-equivalent sugar solution was required for similar activity.

After analysis, the scientists concluded that the vast majority of honey's antibacterial properties come from that protein. This information also sheds light on the inner workings of honey bee immune systems, which may one day help breeders create healthier and heartier honey bees.

http://www.fasebj.org/cgi/content/abstract/24/7/2576

Cholesterol's Other Way out ....

Researchers lead by Mark Brown of Wake Forest University School of Medicine, have come up with an interesting finding that is "there is more than one way to get rid of that cholesterol, which can otherwise lead to atherosclerosis and heart disease".

A model of cholesterol loss first proposed way back in the 1920s suggested the existence of a route that didn't rely on bile. And indeed, studies in dogs unable to get cholesterol into bile showed that the animals actually experienced an increase in cholesterol loss. More recent studies in mice showed a similar thing.  Even so, the researchers said that an alternative pathway has largely been ignored. As a result, scientists have made very little progress in defining the molecular pathways and players involved.

Now, Brown and his colleagues offer new evidence that helps support and clarify this alternate path for cholesterol. Researchers report that mice made unable to secrete cholesterol into bile through genetic manipulation or surgery still lose cholesterol through the feces at a normal rate. Macrophages in those animals also continued to take up cholesterol from blood vessels. The researchers believe that alternate path delivers cholesterol from the liver to the intestine directly through the bloodstream.

     "The classic view of reverse cholesterol transport involved the delivery of peripheral cholesterol via HDL to the liver for secretion into bile," the researchers wrote. "In parallel, we believe that the liver also plays a gatekeeper role for nonbiliary fecal sterol loss by repackaging peripheral cholesterol into nascent plasma lipoproteins that are destined for subsequent intestinal delivery."

For the purposes of cholesterol-lowering drug discovery, it may prove fruitful to consider those two pathways as "separate and compel", claims the lead researcher.

Researchers claims that the drugs aimed to increase cholesterol loss without relying on bile will have fewer side effects (an excess of cholesterol in bile can lead to gallstones). Let us be optimistic and hope for the best, in the near future...

Ref : http://www.cell.com/cell-metabolism/abstract/S1550-4131%2810%2900186-5

Anti-Cancer Effects of Broccoli Ingredient Explained......

In continuation of my update on the dietary benefits of broccoli and how it helps to reduce the cancer risk....

Researchers writing in BioMed Central's open access journal Molecular Cancer have found that sulforaphane, a chemical found in broccoli, interacts with cells lacking a gene called PTEN to reduce the chances of prostate cancer developing.

Richard Mithen, from the Institute of Food Research, an institute of BBSRC, worked with a team of researchers on Norwich Research Park, UK, to carry out a series of experiments in human prostate tissue and mouse models of prostate cancer to investigate the interactions between expression of the PTEN gene and the anti cancer activity of sulforaphane.

"PTEN is a tumour suppressor gene, the deletion or inactivation of which can initiate prostate carcinogenesis, and enhance the probability of cancer progression. We've shown here that sulforaphane has different effects depending on whether the PTEN gene is present."

The research team found that in cells which express PTEN, dietary intervention with SF has no effect on the development of cancer. In cells that don't express the gene, however, sulforaphane causes them to become less competitive, providing an explanation of how consuming broccoli can reduce the risk of prostate cancer incidence and progression.

Ref :  http://www.molecular-cancer.com/content/pdf/1476-4598-9-189.pdf

Predator-released hydrocarbons repel oviposition by a mosquito - nature's insect repellents ?

                                                                   N-Heneicosane 

                                                                    N-Tricosane

Many animals use chemicals to communicate with each other. Pheromones (most of us are familiar with these class of semi-synthetic compounds-used mainly as insect repellents) which influence social and reproductive behaviors within a particular species, are probably the best known and studied. Kairomones are produced by an individual of one species and received by an individual of a different species, with the receiving species often benefiting at the expense of the donor.

Cohen and his Israeli colleagues focused on the interaction between two insect species found in temporary pools of the Mediterranean and the Middle East: larvae of the mosquito C. longiareolata and its predator, the backswimmer N. maculata. When the arriving female mosquitoes detect a chemical emitted by the backswimmer, they are less likely to lay eggs in that pool.

To reproduce conditions of temporary pools in the field, the researchers used aged tap water with fish food added as a source of nutrients. Individual backswimmers were then placed in vials containing samples of the temporary pools, and air samples were collected from the headspace within the vials. The researchers used gas chromatography-mass spectrometry to analyze the chemicals emitted by the backswimmers.

Cohen and his colleagues identified two chemicals, hydrocarbons called n-heneicosane and n-tricosane (see structures), which repelled egg-laying by mosquitoes at the concentrations of those compounds found in nature. Together, the two chemicals had an additive effect.

Since the mosquitoes can detect the backswimmer's kairomones from above the water's surface, predator-released kairomones can reduce the mosquito's immediate risk of predation, says Cohen. But they also increase the female mosquito's chance of dying from other causes before she finds a pool safe for her to lay her eggs in.

Researchers conclude that, these newly identified compounds, and others that remain to be discovered, might be effective in controlling populations of disease-carrying insects. It's far too soon to say, but there's the possibility of an advance in the battle against infectious disease.

http://www3.interscience.wiley.com/journal/123572945/abstract?CRETRY=1&SRETRY=0

Cashew Seed Extract an Effective Anti-Diabetic ?

Cashew seed extract (hydroethanolic extract) shows promise as an effective anti-diabetic, according to a new study from the University of Montreal (Canada) and the Université de Yaoundé (Cameroun). The investigation analyzed the reputed health benefits of cashew tree products on diabetes, notably whether cashew extracts could improve the body's response to its own insulin.

The researchers claims that hydroethanolic extract of cashew seed (CSE) and its active component, anacardic acid (see structure), stimulated glucose transport into C2C12 myotubes in a concentration-dependent manner. Extracts of other parts (leaves, bark and apple) of cashew plant were inactive. Significant synergistic effect on glucose uptake with insulin was noticed at 100 g/mL CSE. CSE and AA caused activation of adenosine monophosphate-activated protein kinase in C2C12 myotubes after 6 h of incubation. No significant effect was noticed on Akt and insulin receptor phosphorylation. Both CSE and AA exerted significant uncoupling of succinate-stimulated respiration in rat liver mitochondria.

"Of all the extracts tested (out of leaves, bark, seeds and apples), only cashew seed extract significantly stimulated blood sugar absorption by muscle cells," says senior author Pierre S. Haddad, a pharmacology professor at the University of Montreal's Faculty of Medicine. "Extracts of other plant parts had no such effect, indicating that cashew seed extract likely contains active compounds, which can have potential anti-diabetic properties."

Researchers conclude that, activation of adenosine monophosphate-activated protein kinase by CSE and AA likely increases plasma membrane glucose transporters, resulting in elevated glucose uptake. In addition, the dysfunction of mitochondrial oxidative phosphorylation may enhance glycolysis and contribute to increased glucose uptake. These results collectively suggest that CSE may be a potential anti-diabetic nutraceutical.

Cashew tree products have long been reported to be effective anti-inflammatory agents, counter high blood sugar and prevent insulin resistance among diabetics. This study validates the traditional use of cashew tree products in diabetes and points to some of its natural components that can serve to create new oral therapies...

Ref  : http://www3.interscience.wiley.com/journal/123573729/abstract?CRETRY=1&SRETRY=0

Discovery of a Proneurogenic, Neuroprotective Chemical.....

Scientists from University of Texas Southwestern Medical Center, Dallas, lead by Dr.Steven McKnight,  have discovered a compound (see structure)  that restores the capacity to form newmemories in aging rats, likely by improving the survival of newborn neurons in the brain's memory hub. The research has turned up clues to a neuroprotective mechanism that could lead to a treatment for Alzheimer's disease.

"This neuroprotective compound, called P7C3, holds special promise because of its medication-friendly properties. It can be taken orally, crosses the blood-brain barrier with long-lasting effects, and is safely tolerated by mice during many stages of development." claims Dr.Steven McKnight

In hopes of finding compounds that might protect such vulnerable neurons during this process, Pieper, McKnight and colleagues tested more than 1000 small molecules in living mice. One of the compounds, designated P7C3 (see structure), corrected deficits in the brains of adult mice engineered to lack a gene required for the survival of newborn neurons in the hippocampus. Giving P7C3 to the mice reduced programmed death of newborn cells,  normalizing stunted growth of branch-like neuronal extensions and thickening an abnormally thin layer of cells by 40 percent. Among clues to the mechanism by which P7C3 works, the researchers discovered that it protects the integrity of machinery for maintaining a cell's energy level.

To find out if P7C3 could similarly stem aging-associated neuronal death and cognitive decline, the researchers gave the compound to aged rats. Rodents treated with P7C3 for two months significantly outperformed their placebo-treated peers on a water maze task, a standard assay of hippocampus-dependent learning. This was traced to a three fold higher-than-normal level of newborn neurons in the dentate gyrus of the treated animals. Rats were used instead of mice for this phase of the study because the genetically engineered mice could not swim.

Prolonged treatment of aged rats with P7C3 also enhanced the birth of new neurons. "Aged rats normally show a decline in neurogenesis associated with an inability to form new memories and learn tasks," Pieper explained..

In their study, rats treated with P7C3 each day showed evidence of an increase in the formation of newborn neurons and significant improvements in their ability to swim to the location of a missing platform, s standardized test of larning and memory in rats.

The key to the treatment's success is the protection of newborn neurons, the researchers report. In fact, they explained, the normal process by which newborn neurons are incorporated into the brain as mature cells is a long and perilous one. Notably, they say that two other drugs (Dimebon and Serono compounds) -- both of which bear structural similarities to P7C3 -also encourage the growth of new neurons. It's tempting to think that all three compounds work in the same way the researchers pinpointed a derivative of P7C3, called A20, which is even more protective than the parent compound. They also produced evidence suggesting that two other neuroprotective compounds eyed as possible Alzheimer's cures may work through the same mechanism as P7C3. The A20 derivative proved 300 times more potent than one of these compounds currently in clinical trials for Alzheimer's disease. This suggested that even more potent neuroprotective agents could potentially be discovered using the same methods. Following up on these leads, the researchers are now searching for the molecular target of P7C3 -  key to discovering the underlying neuroprotective mechanism.

Ref : http://www.cell.com/retrieve/pii/S0092867410006720

Plant extract may be effective against inflammatory bowel disease

In continuation of my update on Broccoli and other Brassica family...
Plant extract may be effective against inflammatory bowel disease

How Dietary Supplement (Broccoli, Cabbage) May Block Cancer Cells....

In continuation of  how dietary supplement may block cancer cells... In my earlier blogs,  I have mentioned that, natural compound formed during the autolytic breakdown of glucobrassicin present in food plants of the Brassica genus, including broccoli, cabbage, Brussels sprouts, cauliflower and kale) are responsible for the anticancer activity associated with broccoli and other Brassica genus.

Now researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James) have discovered how a substance  (see below structure) that is produced when eating broccoli and Brussels sprouts can block the proliferation of cancer cells.

Compelling evidence indicates that the substance, indole-3-carbinol [(above structure, I3C) : Glucobrassicin (right structure) is a type of glucosinolate that can be found in almost all cruciferous plants, such as cabbages  and broccoli, degradation by the enzyme myrosinase is expected to produce an isothiocyanate, indol-3-ylmethylisothiocyanate- which is unstable and hydrlyses to give, I3C, as most dominant degradation product], may have anticancer effects and other health benefits, the researchers say. These findings show how I3C affects cancer cells and normal cells.

The laboratory and animal study discovered a connection between I3C and a molecule called Cdc25A, which is essential for cell division and proliferation. The research showed that I3C causes the destruction of that molecule and thereby blocks the growth of breast cancer cells.

"Cdc25A is present at abnormally high levels in about half of breast cancer cases, and it is associated with a poor prognosis," says study leader Xianghong Zou, assistant professor of pathology at the Ohio State University Medical Center.

For this study, Zou and his colleagues exposed three breast cancer cell lines to I3C. These experiments revealed that the substance caused the destruction of Cdc25A. They also pinpointed a specific location on that molecule that made it susceptible to I3C, showing that if that location is altered (because of a gene mutation), I3C no longer causes the molecule's destruction.

Last, the investigators tested the effectiveness of I3C in breast tumors in a mouse model. When the substance was given orally to the mice, it reduced tumor size by up to 65 percent. They also showed that I3C had no affect on breast-cell tumors in which the Cdc25A molecule had a mutation in that key location.

Ref :  American Association for Cancer Research : Cancer Prevention Research, Xianghong Zou et al.,

Antihypertensive Drugs May Protect Against Alzheimer's Disease....

Researchers at Mount Sinai School of Medicine have found that the drug carvedilol (see structure), currently prescribed for the treatment of hypertension, may lessen the degenerative impact of Alzheimer's Disease and promote healthy memory functions.  

"These studies are certainly very exciting, and suggest for the first time that certain antihypertensive drugs already available to the public may independently influence memory functions while reducing degenerative pathological features of the Alzheimer’s disease brain," said study author Giulio Maria Pasinetti, MD, PhD, Saunders Family Professor of Neurology and Director of the Center of Excellence for Novel Approaches to Neurotherapeutics at Mount Sinai School of Medicine....

Dr. Pasinetti’s team found for the first time that carvedilol, a blood pressure lowering agent, is capable of exerting activities that significantly reduce Alzheimer’s disease-type brain and memory degeneration. This benefit was achieved without blood pressure lowering activity in mice genetically modified to develop Alzheimer’s disease brain degeneration and memory impairment.

They also found that carvedilol treatment was capable of promoting memory function, based on assessments of learning new tasks and information and recall of past information, which is already chemically stored in the brain. In the study, one group of mice received carvedilol treatment and the other group did not. The scientists conducted behavioral and learning tests with each group of mice, and determined that it took the mice in the carvedilol significantly less time to remember tasks than the other group.

Ongoing clinical research is in progress to test the benefits of carvedilol, which may prove to be an effective agent in the treatment of symptoms of Alzheimer’s disease,   hope they will come out with positive results...

Ref : http://www.j-alz.com/issues/21/vol21-2.html

Ingredient in red wine may prevent some blinding diseases

In continuation of my update on Resveratrol.......
Ingredient in red wine may prevent some blinding diseases

Palladium-Catalyzed Trifluoromethylation of Aryl Chlorides..

When I  was working with one of the leading agrochemicals company, I was using 4-chlorobenzotriflouride as starting material for my two projects (trifluralin and a pyrazole derivative with diflouromethyl substituted phnyl).  I know how difficult is to introduce the triflouromethyl group (use of anhydrous HF to convert CCl3 to CF3) and that is why we got the starting material imported. 

Now, MIT chemists have designed a new way to attach a trifluoromethyl group to certain compounds, which they believe could allow pharmaceutical companies to create and test new drugs much faster and potentially reduce the cost of drug discovery. 

MIT Chemistry Professor Stephen Buchwald, who led the research team, says achieving the synthesis has been a long-standing challenge for chemists. "Some people said it couldn't be done, so that's a good reason to try," says Buchwald, the Camille Dreyfus Professor of Chemistry at MIT.

With the new reaction, the CF₃ group can be added at a much later stage of the overall drug synthesis. The reaction can also be used with a broad range of starting materials, giving drug developers much more flexibility in designing new compounds.  Though many groups are trying, the major challenge has been finding a suitable catalyst  to transfer the CF₃ entity from another source to the carbon ring. 

CF₃^- (trifluoromethyl negative ion) tends to be unstable when detached from other molecules, so the catalyst must act quickly to transfer the CF₃ group before it decomposes. The MIT team chose to use a catalyst built from palladium i.e., BrettPhos (see structure). MIT team is not the first to try palladium catalysis for this reaction, but the key to their success was the use of a ligand (a molecule that binds to the metal to stabilize it and hasten the reaction) called BrettPhos 2-(Dicyclohexylphosphino)-3,6-dimethoxy-2'-4'-6'-tri-i-propyl-1,1'-biphenyl,  which they had previously developed for other purposes. 

During the reaction, a CF₃ group is transferred from a silicon carrier to the palladium, displacing a chlorine atom. Subsequently, the aryl-CF₃ unit is released and the catalytic cycle begins anew. The researchers tried the synthesis with a variety of aryl compounds and achieved yields ranging from 70 to 94 percent of the trifluoromethylated products. 

Researchers conclude that, in its current state the process is too expensive for manufacturing use. For drug discovery, however, it may lower overall costs because it streamlines the entire synthesis process.

"For discovery chemistry, the price of the metal is much less important," says Kinzel....

Ref :  http://www.sciencemag.org/cgi/content/abstract/328/5986/1679

Blueberry consumption is beneficial for hepatic diseases....

We know that blueberry has many chemicals such as anthocyanins, proanthocyanidins, resveratrol, flavonols and tannins and how blueberry inhibit mechanisms of cancer cell development and inflammation in vitro. Similar to red grape, some blueberry species contain in their skins significant levels of resveratrol a phytochemical. 

Now research team led by Ming-Liang Cheng, MD, from Department of Infectious Diseases, Guiyang Medical College, Guiyang,  have found that blueberries could reduce liver indices, serum levels of hyaluronic acid and alanine aminotransferase, and increase levels of superoxide dismutase and decrease levels of malondialdehyde in liver homogenates compared with the model group.  Meanwhile, the stage of hepatic fibrosis was significantly weakened. Blueberries increased the activity of glutathione-S-transferase in liver homogenates and the expression of Nrf2 and Nqo1 compared with the normal group, but there was no significant difference compared with the model group. 

The authors suggest that blueberry consumption is beneficial for hepatic diseases (including fibrosis)....

I read an article in the same lines, where in the  researchers from Miyazaki prefecture of southern Japan and University of Miyazaki, screened nearly 300 different agricultural products for potential compounds that suppress HCV replication and uncovered a strong candidate in the leaves of rabbit-eye blueberry (native to the southeastern US). They purified the compound and identified it as proanthocyandin (a polyphenol similar to the beneficial chemicals found in grapes and wine). While proanthocyandin can be harmful, Kataoka and colleagues noted its effective concentration against HCV was 100 times less than the toxic threshold. The researchers are  hoping to explore the detailed mechanisms of how this chemical stops HCV replication....

Ref :  http://www.biologynews.net/archives/2009/08/07/the_hepatitis_healing_power_of_blueberry_leaves.html

Liquid Crystals - A New Way to Better Data Storage ?

In continuation of my update on liquid crystals (after a long gap)....

As cell phones and computers continue to shrink, many companies are seeking better ways to store hundreds of gigabytes of data in small, low-power devices. A special type of liquid crystal (similar to those used in computer displays and televisions) offers a solution  and lasers can encode data throughout a liquid crystal known as holographic storage, the technique makes it possible to pack much more information in a tiny space.   

But attempts to use liquid crystals for data storage have had limited success. In order to reliably record and rewrite data, researchers must figure out a way to uniformly control the orientation of liquid crystal molecules as the most liquid crystal technologies currently rely on physical or chemical manipulation, such as rubbing in one direction, to align molecules in a preferred direction. 

In an important advance, scientists at the Tokyo Institute of Technology have created a stable, rewritable memory device that exploits a liquid crystal property called the "anchoring transition". Researchers  demonstrated memory and rewritable bistable devices based on an anchoring transition of a nematic liquid crystal on a perfluoropolymer surface. Spontaneous orientation changes between planar and homeotropic occur on cooling and heating with a large temperature hysteresis. Orientation switching also occurs by applying an electric field with a response time of several milliseconds depending on the field strength claims the researchers.

Using either a laser beam or an electric field, the researchers can align rod-like liquid crystal molecules in a polymer. Their tests show that the liquid crystal created by the team can store data, be erased and used again...

"This is the first rewritable memory device utilizing anchoring transition," said Hideo Takezoe, who led the research. And because the device is bi-stable -- the liquid crystals retain their orientation in one of two directions -- it needs no power to keep images, adds Takezoe.

 Ref : http://jap.aip.org/japiau/v107/i12/p123108_s1?isAuthorized=no

Resveratrol in Red Wine Neutralizes Toxicity of Proteins Related to Alzheimer's

We know that, Resveratrol (found in the skin of red grapes and is a constituent of red wine, see structure)  (trans-resveratrol) is a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi.  And also it has been reported to possess diverse activities such as, anti-cancer, anti-inflammatory, blood-sugar-lowering and other beneficial cardiovascular effects in mouse and rat models of testings. In the only positive human trial, extremely high doses (3–5 g) of resveratrol in a proprietary formulation have been necessary to significantly lower blood sugar.Claims of anti-aging effects of the same compounds is to be still established.

Now researchers led by Rensselaer Professor Peter M. Tessier, have come up with an interesting finding i.e., resveratrol - has the ability to neutralize the toxic effects of proteins linked to Alzheimer's disease. 

As per the claims by the researchers, resveratrol picks out the clumps of peptides that are bad and leaves alone the ones that are benign, it helps us to think about the structural differences between the peptide isoforms (different packing arrangements of a particular peptide) Deformations of a particular peptide  the Aβ1-42 peptide,   have been linked to Alzheimer's disease. 

Improperly folded peptides have been shown to collect in accumulations called "plaques (often found near areas of cell death in diseased brain)" within the brain.

Researchers conclude that, though it is not clear that resveratrol is able to cross the blood-brain barrier. However, the molecule has garnered interest in recent years for its potential impact on cancer and aging...

Ref : http://www.jbc.org/content/early/2010/05/28/jbc.M110.133108....