An anti-diabetic drug shows hope for cancer

It is clear that in our world of today, Cancer is a major killer. Although Cancer has been with us throughout the history of mankind, it has become a leading cause of death only in the last century. Prior to 1990, most deaths were due to infectious diseases, such as pneumonia and tuberculosis and life expectancy was less than fifty years. Cancer was a rare disease that accounted for only a small percentage of deaths.

But now times have changed and cancer has gripped our world both quantitatively and qualitatively.So far, no cure for cancer has been found. Treatment of cancer in the initial stages can save the patient’s life but it cannot prevent it’s recurrence. Also, some cancers do not respond to treatments at all and end up killing the host. What the medical world requires is further research on the treatment of cancer as well as better and powerful therapies against cancer.

Recently PPAR Ligands have emerged as an effective therapy against cancer. PPAR stands for peroxisome proliferator activated receptor, and are a type of steroid hormone nuclear receptor acting as transcription factors. These have been implicated in a variety of human pathologies but so far their therapeutic use has been limited to the treatment of Type 2 Diabetes where drugs targeting PPAR-gamma are being used to control the diabetes.

For more than a decade, work on PPARs was driven by their important role in the regulation of cellular metabolism, PPAR in tissues known for high -oxidation rates such as liver, heart, muscle, and kidney, while PPAR was mainly studied for its adipogenic activity. At present, they are receiving growing attention for their involvement in the regulation of cell proliferation, death, and differentiation of both normal and malignant cells.

Plasmepsin V gives plasmodium license to kill

When mosquitoes develop in the erythrocytes, they employ hundreds of their protein to terrorize a red blood cell. These proteins then change the mechanics of the cytoskeleton, the way nutrients are taken in by the RBC and also they alter its mechanical stability. 

Proteins destined for export are synthesized in the endoplasmic reticulum (ER) and cleaved at a conserved (PEXEL) motif, which allows translocation into the host cell via an ATP-driven translocon called the PTEX complex. We report that plasmepsin V, an ER aspartic protease with distant homology to the mammalian processing enzyme BACE, recognizes the PEXEL motif and cleaves it at the correct site. This enzyme is essential for parasite viability and ER residence is essential for its function. We propose that plasmepsin V is the PEXEL protease and is an attractive enzyme for antimalarial drug development.

 

 Research paper

Plasmepsin V licenses Plasmodium proteins for export into the host erythrocyte

Ilaria Russo^1,2, Shalon Babbitt^1,3, Vasant Muralidharan^1,3, Tamira Butler¹, Anna Oksman¹ & Daniel E. Goldberg¹

Brain stem Cell transplant

If the kidneys stop functioning, we can go in for a kidney transplant, if the liver degenerates, we can go in for a liver tissue transplant. Then there is Corneal transplant, Pancreatic transplant, Lung transplant, Thymus transplant and so on. Now the question is: Can we go in for brain cell transplant? Can we treat or control the neurodegenerative diseases by simply injecting in new brain cells?

The answer to this question is neither “yes” nor “no”, but “could be”. Yes it could be possible and the scientists are trying hard to change the “could be” to “yes”. The Brain Stem Cell Transplant is the newest possible strategy to treat neurodegenerative disorders wherein stem cells are transplanted into the brain that prevent the existing nerve cells from dying.

According to a recent report co-authored by several international research groups and led by Karolinska Institutet, Sweden,(2010), the mechanism by which these injected brain cells prevent the existing brain from dying is by quickly establishing direct channels called gap junctions to the diseased or threatened nerve cells. These gap junctions allow molecular signals to pass back and forth between the transplanted brain cell and the host brain cell and thus prevent the latter from dying out.

So far, 400 patients worldwide, suffering from Multiple Sclerosis,have shown signs of recovery by this method. A landmark in this area was on Oct 20^th, 2005 when the FDA approved the first Brain Stem Cell Transplant on six Children suffering from Batten Disease, a rare genetic neurodegenerative disorder. Right now, intensive research is on to make Brain stem Cell Transplant, a safe and acceptable mode of treatment.

So far so good. Now looking at the other side, a report published in Nature claims that unregulated brain stem cell transplant can cause brain tumours. Also a research team of MIT, recently claimed that Brain Stem Cell Transplants are more complicated than previously thought because the adult stem cells found in the brain are pre-programmed to make only certain kinds of connections making it impossible for a brain neural cell to be transplanted to the other parts of the brain or spinal cord.

Well, whatever maybe the case, we hope that one day the Brain stem cell transplant does become a reality and help to treat the millions worldwide who  suffer from neurodegenerative diseases, brain damage or stroke.

Riboswitches : A fresh new promise as an anti-bacterial drug targets

There is increasing concern that the current antibacterial drug repertoire includes mainly decades-old chemical scaffolds that target a very narrow spectrum of cellular processes. It is to highlighted that antibiotics drug development has produced only one new chemical scaffold in the past 30 years, and currently prescribed antibiotics collectively disrupt the function of only four bacterial life processes. Perhaps as a consequence, antibiotic resistance is now emerging at an alarmingly rapid pace, with indications that even the most recently approved antibiotics could soon be ineffective. Sustained success in the long-term battle against bacterial pathogens will require the identification of new chemical scaffolds that target other cellular processes. 

One potentially vulnerable process is the regulation of gene expression by metabolite-sensing RNAs called riboswitches.

In many bacteria, the expression of a number of genes crucial to metabolite biosynthesis or transport is regulated by mRNA structures called riboswitches. Typically found in the 5'-untranslated region (5'-UTR) of certain bacterial mRNAs, members of each known riboswitch class form a structured receptor, or 'aptamer', that has evolved to bind to a specific fundamental metabolite. If the cognate metabolite is not present when the 5'-UTR is transcribed, the riboswitch in most cases folds into a structure that does not interfere with the expression of the adjacent open reading frame (ORF). When present at a sufficiently high concentration, the metabolite binds to the riboswitch receptor, which induces the formation of a structure in the nascent mRNA that represses the expression of the ORF. This structure can be a terminator hairpin, which halts RNA synthesis before the ORF can be synthesized or a hairpin that sequesters the Shine-Dalgarno sequence and prevents the ribosome from binding to the mRNA and translating the ORF. Because the gene or group of genes regulated by a riboswitch is usually involved in the synthesis or transport of its cognate metabolite, riboswitches are direct regulators of cellular metabolite concentrations.

In fact, few anti-bacterial drugs previously thought to have a certain mechanism of action are now found to work partly by means of riboswitches. As such riboswitches show a great promise of hope in our fight against the pathogenic microbes. Amen to that.