(Press-News.org) The LSL60101 compound, a specific ligand of the I2-IR receptors in the brain, could shed light on the development of future strategies against Alzheimer's disease. This is stated in the recent studies by the Research Group on Medicinal Chemistry and Pharmacology of Neurodegenerative Diseases of the University of Barcelona, published in the journals European Journal of Medicinal Chemistry and British Journal Pharmacology. In studies carried out with mice, LSL60101 has improved the cognitive deficit and the biomarkers related to the disease in these animal models.
These studies result from the collaboration of the research teams led by professors Carmen Escolano, from the Faculty of Pharmacy and Food Sciences and the Institute of Biomedicine of the UB (IBUB), and Mercè Pallàs, from the same Faculty and the Institute of Neurosciences (UBNeuro). Framed within a program in the CaixaImpulse program, the studies are also signed by the UB researchers Christian Griñán Ferré, Foteinin Vasilopoulou, Sergio Rodríguez Arévalo and Andrea Bagán. Among the participants are teams of the
Alzheimer's is a neurodegenerative disease without a cure yet. Despite the efforts made by the international scientific community, many initiatives in medical chemistry to find future drugs to treat have failed and it is postulated that this situation could be explained by the selection of unsuitable therapeutic targets. Therefore, it is decisive to tackle the fight against Alzheimer's from perspectives that help to shape new therapeutic targets from the side of the innovation in biomedical research.
The paper published in the European Journal of Medicinal Chemistry describes the synthesis of a new family of compounds with high affinity and selectivity for I2 imidazoline receptors, altered in the brain of patients with Alzheimer's. The synthesis pathway of compounds, which is efficient and affordable, would allow to apply different structural modifications to access a notable range of compounds of pharmaceutical interest.
The new family of I2-IR receptor ligands is formed by compounds with different structural features. In particular, the interaction of a representative compound --LSL60101 or garsevil-- with the I2 imidazoline receptors improves the cognitive deficit in murine models with neurodegeneration and Alzheimer's. This compound, described for the first time in the scientific literature in 1995 as a specific I2-IR receptor ligand, outstands for its properties in preclinical studies of pharmacokinetics, metabolism and toxicity, and presents a high affinity and selectivity regarding these receptors in the human brain.
Nowadays, the function of the I2-IR receptors under physiological conditions is unknown. However, researchers know these are altered in some neurodegenerative diseases such as Alzheimer's or Parkinson's. Moreover, the scientific bibliography features studies with ligands of these receptors as markers of the progress of Alzheimer's disease.
"Apart from fighting the formation of amyloid-beta plaques or neurofibrillary tangles, acting on the neuroinflammation mechanisms could be a suitable therapeutic strategy to stop the progression of such a complex disease like Alzheimer's", notes Professor Carmen Escolano.
LSL60101 versus donepezil: the future of a combined therapy
According to the article in British Journal Pharmacology, the effects of LSL60101 in laboratory animals prove to be mor beneficial than those from donepezil, one of the most commercialized drugs for Alzheimer's treatments.
In the murine models with Alzheimer's, "the new compound created changes in oxidative stress markers and in neuroinflammation makers, one of the main dysfunctions present in most of the neurodegenerative diseases. In particular, LSL60101 reduced the number of amyloid-beta plaques and the levels of this altered protein in the brain of the treated animals. Parallelly, it reduced the phosphorylation of the tau protein, another important biomarker in the progression of the diseases", says Professor Mercè Pallàs.
The results could be explained with the several action mechanisms of LSL60101 and donepezil. Donepezil increases the levels of acetylcholine --a neurotransmitter related to memory and cognitive skills-- because it inhibits the enzyme in charge of its degradation (acetylcholinesterase). Also, LSL60101 is described as a I2 imidazoline receptor ligand, which have increased in the brain of people with dementia. Everything points out to the fact that the interaction of this drug with its receptor is involved in the generation of proinflammatory molecules that would increase the ongoing neuroinflammation in the disease. Therefore, I2 ligands would contribute to reduce the inflammation and thus, would slow the progression of the disease.
Both compounds were efficient in the recovery of the cognitive damage, but one of the objectives of the research study was to find whether the combination could improve the success of the treatment. "The results show that the SL60101-donepezil combined therapy is more efficient in some biomarkers of the disease. Therefore, it is possible that, with the combination of the suitable dose, we could reach an additive or even synergic effect", note the researchers.
Conducting new researches in the study will be a decisive factor to focus on the relation between I2 imidazoline receptors and Alhzeimer's and other diseases, and to boost the design of new therapeutic strategies based on the use of new selective I2-IR ligands to modulate the altered receptors in neurodegenerative pathologies.
INFORMATION:
Preschool children are sensitive to the gap between how much they know and how much there is to learn, according to a Rutgers University-New Brunswick study.
The research, published in the journal END ...
Under a concrete drainage culvert at the edge of a town in Botswana, a troop of banded mongoose is getting ready to leave its den. Moving from shade into light, the cat-sized animals scan the area for signs of danger and for opportunities to find something to eat in an increasingly crowded neighborhood.
Unbeknownst to them, the genetics of this troop's members -- and others like them -- are providing researchers in the College of Natural Resources and Environment with new understandings of how and why animal behavior changes in proximity to human development and how that change can impact infectious disease spread.
The researchers used genetic tools to identify changes in movement behavior among mongooses ...
An immunotherapy based on supercharging the immune system's natural killer cells has been effective in treating patients with recurrent leukemia and other difficult to treat blood cancers. Now, researchers at Washington University School of Medicine in St. Louis have shown in preclinical studies conducted in mice and human cells that this type of cell-based immunotherapy also could be effective against solid tumors, starting with melanoma, a type of skin cancer that can be deadly if not caught early.
The study is published June 29 in Clinical Cancer Research, ...
[BRIDGEWATER, NJ; June 29, 2021] The American Association of Feline Practitioners (AAFP) has released the updated 2021 AAFP Feline Senior Care Guidelines to be published in the July issue of the Journal of Feline Medicine and Surgery. This update provides emerging advances in feline medicine with respect to the aging cat. The Task Force of experts provides a thorough current review in feline medicine that emphasizes the individual senior patient.
As defined in the 2021 AAHA/AAFP Feline Life Stage Guidelines, cats over 10 years of age are considered to be 'senior.' Understanding the changing needs of each individual senior cat is critical for both veterinary professionals and cat owners. "Veterinary professionals are encouraged to use the 2021 ...
Osaka, Japan - A team of scientists led by the Department of Applied Physics at Osaka University, the Department of Physics and Electronics at Osaka Prefecture University, and the Department of Materials Chemistry at Nagoya University used photoinduced force microscopy to map out the forces acting on quantum dots in three dimensions. By eliminating sources of noise, the team was able to achieve subnanometer precision for the first time ever, which may lead to new advances in photocatalysts and optical tweezers.
Force fields are not the invisible barriers of science fiction but are a set of vectors indicating the magnitude and direction of forces acting in a region ...
Overview
The research team of Professor Toshihiko Eki of the Department of Applied Chemistry and Life Science (and Research Center for Agrotechnology and Biotechnology), Toyohashi University of Technology used a next-generation sequencer to develop a highly efficient method to analyze soil nematodes by using the 18S ribosomal RNA gene regions as DNA barcodes. They successfully used this method to reveal characteristics of nematode communities that inhabit fields, copses, and home gardens. In the future, the target will be expanded to cover all soil-dwelling organisms in agricultural soils, etc., to allow investigations into a soil's environment and bio-diversity. This is expected to contribute to advanced agriculture.
Details
Similar to when the ...
Receiving a simple thank you, spending time with peers and further developing their expertise, are all factors that make veterinarians feel good at work, according to a new study by researchers at the University of Adelaide.
In the study published by Vet Record, researchers investigated the positive side of veterinary work and specifically what brings vets pleasure in their job.
Lead author Madeleine Clise, a psychologist and Adjunct Lecturer at the University of Adelaide's School of Psychology says: "At a time in Australia when there are national shortages of vets, particularly in regional areas, and increased publicity about the ...
Prolonged exposure to antibiotics leads to the gain of bacteria's ability to defeat the drugs designed to fight them. Thus, if such antibiotic-resistant bacteria cause the infection, the only chance to use a specialized virus called phage infecting specific bacteria species. It is a powerful weapon against deadly diseases. At the same time, the effective treatment depends on factors that would not be suspected for years to impact the successful therapy. Recently, researchers from the Institute of Physical Chemistry, Polish Academy of Sciences led by dr. Jan Paczesny and Professor ...
Tsukuba, Japan - Depression is a worldwide problem, with serious consequences for individual health and the economy, and rapid and effective screening tools are thus urgently needed to counteract its increasing prevalence. Now, researchers from Japan have found that artificial intelligence (AI) can be used to detect signs of depression.
In a study published this month in BMJ Open, researchers from University of Tsukuba have revealed that an AI system using machine learning could predict psychological distress among workers, which is a risk factor for depression. ...
Atomic nuclei contain enormous energy that can be extracted through their fission mechanism, for example, as a result of the radioactive decay of uranium or plutonium nuclei. Likewise, a quantum of light of several electron-volts (2.4 eV in a laser pointer with a green beam) has colossal energy. If all photons were absorbed by matter, then its temperature could reach several thousand degrees. However, in practice this does not happen. The reason is the weak light-matter interaction due to the fact that the wavelength of light (500 nm) is a thousand times larger than the size of an emitting / absorbing atom (0.5 nm). It is this physical mechanism that prevents the destruction of matter when illuminated. The efficiency of light absorption increases ...
