Rethinking of Alzheimer's Disease ?

So for the explanation for the Alzheimer's disease is "amyloid hypothesis", i.e., the disease results from of an accumulation of the peptide amyloid beta, the toxic protein fragments that deposit in the brain and become the sticky plaques that have defined Alzheimer's, this hypothesis has been accepted for 100 years. Something new explanation has been provided by George Bartzokis of UCLA professor of psychiatry and he says that a better working hypothesis is the "myelin model". He explains the model in the following lines :

Like insulation around wires, myelin is a fatty sheath that coats our nerve axons, allowing for efficient conduction of nerve impulses. It is key to the fast processing speeds that underlie our higher cognitive functions and encoding of memories. But the lifelong, extensive myelination of the human brain also makes it uniquely vulnerable to damage. The myelin model's central premise is that it is the normal, routine maintenance and repair of myelin throughout life that ultimately initiates the mechanisms that produce degenerative diseases like Alzheimer's. That is, the amyloid-beta peptide and the tau peptide, which is also implicated in Alzheimer's, as well as the signature clinical signs of the disease, such as memory loss and, ultimately, dementia, are all byproducts of the myelin breakdown and repair processes. The pervasive myelination of our brain is the single most unique aspect in which the human brain differs from other species.

Myelin is produced by oligodendrocytes, specialized glial cells that themselves become more vulnerable with age. Myelination of the brain follows an inverted U-shaped trajectory, growing strongly until our 50s, when it very slowly begins to unravel as we age. The myelin that is deposited in adulthood ensheaths increasing numbers of axons with smaller axon diameters and so spreads itself thinner and thinner. As a result, it becomes more susceptible to the ravages of age in the form of environmental and genetic insults and slowly begins to break down faster than it can be repaired.

The exclusive targeting of the amyloid-beta peptide for many years is understandable because the same genes and enzymes involved in controlling myelination and myelin repair are, ironically, also involved in the production of amyloid-beta proteins. Bartzokis' point is that the amyloid beta may actually develop as a result of the natural process of the repair and maintenance of myelin. So the breakdown that leads to Alzheimer's and other age-related brain diseases, such as Parkinson's, may begin much earlier, before the formation of the protein deposits that are used to define these diseases," Bartzokis said. Hope this explanation will lead to new innovative ideas for drug discoverers like rather than targeting amyloid-beta peptide !. Hoping for the better results....

Ref : http://newsroom.ucla.edu/portal/ucla/new-target-for-alzheimer-s-102065.aspx

Gene Therapy Trial To Treat Alzheimer's Disease !

The first study of its kind for the treatment of patients : the phase II study examines the safety and possible benefits of CERE-110. CERE-110 contains a gene and is injected during surgery into a part of the brain affected by Alzheimer's disease.

The gene will instruct brain cells to produce more of a protein, called Nerve Growth Factor or NGF, which helps nerve cells survive and function properly. The transfer of this gene into the brain is a medical technique called gene therapy. Though the goal is to to stop the progression of Alzheimer's disease, its a good move because still there are drugs to be innovated for the complete cure. Congrats Dr. Chris Kalhorn.

Ref : http://explore.georgetown.edu/news/?ID=44677&PageTemplateID=295

Monolaurin as a microbial agent ?

We know that Coconut oil contains about 40 to 55 percent lauric acid. Lauric acid is the main saturated fatty acid found in coconut fat and in palm kernel oil. Lauric acid is also known as n-dodecanoic acid, which is a saturated medium chain C₁₂-fatty acid, hence the Greek name “dodeca”, meaning twelve. A certain biochemical derivative of lauric acid, monolaurin (see right structure), has proven to be anti-viral, anti-bacterial, and anti-protozoal, both in vitro and in vivo experiments — and monolaurin can destroy lipid-coated viruses, including influenza. Lauric acid, however does not have these properties as strongly as monolaurin. When ingesting coconut oil, only a small percentage—an estimated 3%--of the lauric acid will be transformed by the body into the active monolauric acid. This has been shown to elevate the body’s overall immunity to some degree.

Though there were many companies selling this as a dietery suppliment, now monolaurin has been recognized as safe by the U.S. Food and Drug Administration (FDA) and is known for its antimicrobial properties. If used in combination with other antimicrobial agents, monolaurin can present an effective barrier to microorganisms.

Thanx to the researchers from Zhejiang University in China, who studied the use of monolaurin as a nontraditional preservative in food products by combining it with commonly used antimicrobials in various concentrations and testing it on bacterial strains including Esherichia coli and on food components such as soy protein and water-soluble starch.

The findings are really interesting :

1. Monolaurin combined with ethylenediaminetetraacetic acid (EDTA)，a binding agent, was effective against Esherichia coliand Bacillus subtilis but not Staphylococcus aureus.

2. When combined with the antimicrobial nisin, monolaurin was synergistically effective against all three bacteria.

3. Antibacterial effectiveness was reduced by fat or starch but was not affected by protein.

Congrats for this achievement...

Ref : http://www.ift.org/cms/?pid=1002122

Current Hepatitis C Treatments................

Current Hepatitis C Treatments Work Equally Well, Researchers Report

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New Antituberculosis Compounds ?

We all know how TB has become a pandemic and several attempts to eradicate the disease have been tried and scientists are still finding new ways. However the most disadvantage part for the scientists lies in the fact that "the disease-causing bacteria have a sophisticated mechanism for surviving dormant in infected cells". i.e., TB bacteria have a sophisticated way to remove the damaged proteins — a protein-cleaving complex known as a proteasome — identified in earlier research by the Nathan lab. By breaking down damaged proteins, the proteasome allows the bacteria to remain dormant, and possibly go on to cause active TB. And hence finding drugs to disable the proteasome would be a new way to fight TB.

In developing proteasome-inhibitor drugs, scientists face several hurdles. A significant one is the fact that human cells also possess proteasomes, which are essential to their survival. To be effective, the drugs would have to specifically target the TB proteasome without adversely affecting the human protein-cleanup complex.

This study represents a shift in strategy for designing antibiotics that treat TB, says Dr. Lin (Assistant Research professor of Microbiology and Immunology at Weill Cornell Medical College). All the groups who tried focused on developing drugs that attacked the bacterium in its active phase, but this group has found a compound that may help to destroy it in its dormant stage.

The Weill Cornell team screened 20,000 compounds for TB proteasome inhibition activity. They identified and synthesized a group of inhibitors, which they then tested for their ability to inhibit the proteasome inside the mycobacteria. They also tested the compounds' effect on monkey epithelial cells and human immune system cells in culture. After reading this article, I could recollect the High Throughput Screening of my compounds (Southern Research Institute, Birmingham).  The newly synthesized compounds are specific, less toxic, more active and more over the inhibition of the TB proteasome is irreversible and about 1,000-fold more effective than the minor inhibition observed against human proteasomes.

The structural studies revealed that the inhibitor molecules block the proteasome's ability to degrade proteins in more than one way: by producing a direct chemical change to the proteasome active site, and by altering the conformation of the "pocket" into which protein fragments bind before being degraded. Congrats for this efforts and all the best for their future endeavor.... More....

New Marker For Alzheimer's Discovered

New Marker For Alzheimer's Discovered

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Genetic Hint For Ridding The Body Of Hepatitis C

Genetic Hint For Ridding The Body Of Hepatitis C

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New Rabies Vaccine May Require Only A Single Shot... Not 6 !

People were really scared about the number of injections (it used to varies from 12 to 6) rather than the real pain of the dog's bite. Now thanks to Dr. McGettigan according to the researchers, a replication-deficient rabies virus vaccine that lacks a key gene called the matrix (M) gene induced a rapid and efficient anti-rabies immune response in mice and non-human primates.

The M gene is one of the central genes of the rabies virus, and its absence inhibits the virus from completing its life cycle. The virus in the vaccine infects cells and induces an immune response, but the virus is deficient in spreading. The immune response induced with this process is so substantial that only one inoculation may be sufficient enough both pre-exposure and post-exposure settings. The details will be published in the forth coming journal of infectious disease (J Infect Dis.).

Congrats, Dr.McGettigan and co-workers.