Researchers design new substances that might help fight Alzheimer's and Parkinson's disease

June 13, 2012

University of Granada researchers have tested melatonin analogues in rats that inhibit the enzyme nitric oxide synthase, which is involved in the development of the diseases referred above.

This enzyme is also involved in other conditions as or rheumatoid arthritis, as well as in neurodegenerative conditions as Huntington's disease and .

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, or , as well as in 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. Most of the results obtained in this study have been published in .

Melatonin is a hormone secreted by the pineal gland that inhibits the 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 ".

New Inhibitors

The University of Granada researchers that participated in this study work at the Department of Pharmaceutical and and the Institute of Biotechnology of the University of Granada. 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.

Explore further: Preclinical study links gene to brain aneurysm formation

Related Stories

What effect does melatonin have in colitis?

March 18, 2008

In rats with experimental colitis, the marked increase in bacterial translocation in postcolitis rats has been reversed by melatonin administration. This is due to melatonin's anti-inflammatory and anti-apoptotic effects.

Why salad helps you say yes to 'NO'

March 23, 2011

Disorders of the circulatory system- vascular diseases- are common in the developed world, and can lead to heart attacks, strokes and even death. However, treatments for these disorders, such as bypass surgery and angioplasty, ...

Reversing smoke-induced damage and disease in the lung

October 13, 2011

By studying mice exposed to tobacco smoke for a period of months, researchers have new insight into how emphysema and chronic obstructive pulmonary disease (COPD) develops. In the October 14th issue of Cell they also report ...

'Moonlighting' enzyme unravels arginine paradox

November 13, 2011

(Medical Xpress) -- Nearly 20 years ago, the journal Science tagged nitric oxide as the "molecule of the year." Since that time, researchers have tried to study and target this simple molecule that is involved in virtually ...

Recommended for you

Basic research fuels advanced discovery

August 26, 2016

Clinical trials and translational medicine have certainly given people hope and rapid pathways to cures for some of mankind's most troublesome diseases, but now is not the time to overlook the power of basic research, says ...

New avenue for understanding cause of common diseases

August 25, 2016

A ground-breaking Auckland study could lead to discoveries about many common diseases such as diabetes, cancer and dementia. The new finding could also illuminate the broader role of the enigmatic mitochondria in human development.

New method creates endless supply of kidney precursor cells

August 25, 2016

Salk Institute scientists have discovered the holy grail of endless youthfulness—at least when it comes to one type of human kidney precursor cell. Previous attempts to maintain cultures of the so-called nephron progenitor ...

Strict diet combats rare progeria aging disorders

August 25, 2016

Mice with a severe aging disease live three times longer if they eat thirty percent less. Moreover, they age much healthier than mice that eat as much as they want. These are findings of a joint study being published today ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.