University of Granada researchers have tested melatonin analogues in rats that inhibit the enzyme nitric oxide synthase, which is involved in the development of Alzheimer’s and Parkinson’s disease.

This enzyme is also involved in other conditions as inflammatory bowel disease or rheumatoid arthritis, as well as in neurodegenerative conditions as Huntington’s disease and amyotrophic lateral sclerosis.

University of Granada researchers have tested melatonin analogues in rats as it inhibits the enzyme nitric oxide synthase (NOS), which is involved in the development of conditions as inflammatory bowel disease, septic shock or rheumatoid arthritis, as well as in neurodegenerative conditions as Huntington’s disease, Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis.

Some of the new analogues developed by the University of Granada have been tested in vivo in rats and present “very interesting pharmacological properties, as they are much more efficient than melatonin” in inhibiting NOS activity in Parkinson models.

Melatonin is a hormone secreted by the pineal gland that inhibits the central nervous system in rats and humans. Therefore, it is said to have neuroprotective and anticonvulsant properties. These properties give melatonin the ability to inhibit nitric oxide production, as NO is involved in numerous physiological and pathological processes. Therefore, it is necessary to regulate NO production. At present, researchers are trying to “develop powerful and selective inhibitors of each NOS isoform, which would allow clinicians to control specific pathologies, and would help determine the role of the different isoforms in the biological system”.

Taking melatonin as a model, the researchers designed and synthesized several families of complexes (kynurenines, kynurenamines and phenyl pyrazolines), which act as NOS inhibitors. The comparative analysis of the structures of these three families of complexes “allows us to determine structure-activity relationships to inhibit the enzyme NOS and develop a model that might be used to design new inhibitors of this enzyme”, the researchers state.

Nitric oxide is a very reactive enzyme, has a relatively long mean life and is a non-polar substance, i.e.it easily passes through cell membranes to spread to other tissues and reacts with many different molecules. In addition, it is an important signaling molecule involved in many physiological processes as neurotransmission, blood circulation and pressure, platelet aggregation and inflammation.

A number of studies have confirmed that each NOS isoform is involved in different biological roles. Thus, nNOS is mainly expressed in neural tissue and plays a major role in the production of NO as neurotransmitter; eNOs is mainly found in the vascular endothelium, where it regulates blood pressure and vascular tone.The enzyme iNOS –which expression is mainly induced by activated macrophages and other types of cells is involved in the body defense system. Finally, the mitochondrial isoforms c-mtNOS and i-mtNOS are involved in NO production within the cell and control cell bioenergetics.

written by Bioenergetics

A new and unexpected role for RNA is identified: the defence of genome integrity and stability. A study published in the scientific journal Natureshows that an until now unknown class of RNA — the newly christened DDRNA — plays a key role in activation of the molecular alarms necessary to safeguard our genome when DNA damage from internal or external factors occurs.

The discovery described in the pages of Nature emerges from a study conducted by Fabrizio d’Adda di Fagagna at IFOM in Milan, in collaboration with the CNR in Pavia, the IIT at the IFOM-IEO in Milan and the Riken Omics Science Center in Yokohama, Japan.

Given the importance of the cellular DNA damage response in aging, in the repression and control of tumour development, and in therapeutic treatments for cancer, the discovery could open promising interpretive and potentially therapeutic perspectives.

For decades the scientific community has attributed a role to RNA that is subordinate to that of DNA: the functional processes of expression of genetic information into proteins. With some known exceptions, such as the classes of tRNA and rRNA involved in the synthesis of proteins, RNA molecules were considered “fleeting” messengers necessary to carry genetic instructions from the nucleus, site of the genome, to the cytoplasm where proteins, the scaffolding of living organisms, are produced.

written by Bioenergetics

If you’ve traveled to a forested national park out West in recent years, you may have noticed two things. First, a growing number of lodgepole pine trees are dying, victims of the bark beetle. And secondly, atmospheric haze, caused in part by tiny solid particles suspended in the air, is becoming a problem.

A study by a researcher at Southern Illinois University Carbondale shows these two phenomena may be related, tied together by chemistry and climate change factors.

Kara Huff Hartz, assistant professor of chemistry and biochemistry in the College of Science, has authored a study appearing May 23 in the journal Environmental Science & Technology, a division of the American Chemical Society. The study, which Huff Hartz conducted by collecting gas specimens from bark beetle-infested and non-infested lodgepole pines, shows a large increase in the gases given off by the beetle infestations, which could enhance airborne particulate matter problems and haze in the area.

written by Bioenergetics