Acetyltransferases (HATs) as Targets for Neurological Therapeutics

The acetylation of histone and non-histone proteins controls a great deal of cellular functions, thereby affecting the entire organism, including the brain. Acetylation modifications are mediated through histone acetyltransferases (HAT) and deacetylases (HDAC), and the balance of these enzymes regulates neuronal homeostasis, maintaining the pre-existing acetyl marks responsible for the global chromatin structure, as well as regulating specific dynamic acetyl marks that respond to changes and facilitate neurons to encode and strengthen long-term events in the brain circuitry (e.g., memory formation). Unfortunately, the dysfunction of these finely-tuned regulations might lead to pathological conditions, and the deregulation of the HAT/HDAC balance has been implicated in neurological disorders. During the last decade, research has focused on HDAC inhibitors that induce a histone hyperacetylated state to compensate acetylation deficits. The use of these inhibitors as a therapeutic option was efficient in several animal models of neurological disorders. The elaboration of new cell-permeant HAT activators opens a new era of research on acetylation regulation. Although pathological animal models have not been tested yet, HAT activator molecules have already proven to be beneficial in ameliorating brain functions associated with learning and memory, and adult neurogenesis in wild-type animals. Thus, HAT activator molecules contribute to an exciting area of research.     

Community Led Co-Design of a Social Networking Platform with Adolescents with Autism Spectrum Disorder

Journal of Autism and Developmental Disorders - Adolescents with ASD face challenges in forming positive friendships due to their ASD condition. This study developed a social networking platform...     

Low Concentration of a Dioxin (2, 3, 7, 8 TCDD) Affects the Glycosidases and Acid Phosphatase Activity in Mice Hepatocytes

Present communication reports the effects of environmentally available, low doses of tetra chloro di benzo-p-dioxin (2,3,7,8 TCDD) to lysosomal enzymes in mice liver. The study tests the hypothesis, in vivo exposure of low dose TCDD provokes dose and duration dependent toxic effects to key lysosomal enzymes and thereby causes cellular apoptotic changes. Three groups of female Swiss albino mice were subjected to two doses of TCDD (0.004 mg/kg bw/d, 0.04 mg/kg bw/d) for 2, 4 and 6 days of exposure durations. The results indicated significant exposure duration dependent effects of TCDD in mice liver cells. The results suggested that TCDD possibly induced an increase in intracellular ions or ROS which in turn altered different physiological activities by affecting different metabolic pathway of the liver cells. The altered functions of key lysosomal enzymes by TCDD may also evoke the process of cellular apoptosis.     

Andrographolide inhibits human serum albumin fibril formations through site-specific molecular interactions

Protein misfolding and fibrillation are the fundamental traits in degenerative diseases like Alzheimer''s, Parkinsonism, and diabetes mellitus. Bioactives such as flavonoids and terpenoids from plant sources are known to express protective effects against an array of diseases including diabetes, Alzheimer''s and obesity. Andrographolide (AG), a labdane diterpenoid is prescribed widely in the Indian and Chinese health care systems for classical efficacy against a number of degenerative diseases. This work presents an in depth study on the effects of AG on protein fibrillating pathophysiology. Thioflavin T fluorescence spectroscopy and DLS results indicated concentration dependent inhibition of human serum albumin (HSA) fibrillation. The results were confirmed by electron microscopy studies. HSA fibril formations were markedly reduced in the presence of AG. Fluorescence studies and UV-Vis experiments confirmed further that AG molecularly interacts with HSA at site. In silico molecular docking studies revealed hydrogen bonding and hydrophobic interactions with HSA in the native state. Thus AG interacts with HSA, stabilizes the native protein structure and inhibits fibrillation. The results demonstrated that the compound possesses anti-amyloidogenic properties and can be promising against some human degenerative diseases.

Andrographolide inhibited HSA protein fibrillation through site specific interactions.     

Purification and Characterization of Alkaline Protease from Bacillus sp. HD292

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Proteolytic enzymes form a very significant group of enzymes which are used for a variety of purposes...     

Community-Based Treatment for Youth with Co- and Multimorbid Disruptive Behavior Disorders

Little is known about the types of psychotherapeutic practices delivered to youth with comorbid and multimorbid diagnoses in community settings. The present study, based on therapists’ self-reported practices with 569 youth diagnosed with a disruptive behavior disorder (ODD or CD), examined whether specific therapeutic practice applications varied as a function of the number and type of comorbid disorders. While type of comorbid disorder (AD/HD or internalizing) did not predict therapists’ practices, youth with more than two diagnoses (multimorbid) received treatment characterized by a more diverse set and a higher dosage of practices.     

Drug Discovery Research in India: Current State and Future Prospects

Indian civilization developed a strong system of traditional medicine and was one of the first nations to develop a synthetic drug. In the postindependence era, Indian pharmaceutical industry developed a strong base for production of generic drugs. Challenges for the future are to give its traditional medicine a strong scientific base and develop research and clinical capability to consistently produce new drugs based on advances in modern biological sciences.Indian civilization is one of the few in the world that developed a full-fledged system of traditional medicine. The approach of Indian traditional medicine, e.g., the ayurvedic system, is herbal based in general and is more effective for chronic diseases and prevention. Although modern medicine has found its own niche in India, traditional formulations are still widely used, and more and more scientifically validated formulations are appearing in the market. In recent times, many plants used in Indian system of medicine have been analyzed by modern analytical methods and active components have been isolated. Significant amount of medicinal chemistry efforts are going on around these molecules in an attempt to develop more potent leads. These include curcumin from turmeric,¹ Bacosides from Brahmi (Bacopa monnieri),² and Forskolin from Coleus forskohlii. The first modern synthetic drug to be developed in India was Urea Stibamine in 1922 by UN Brahmachari against visceral leishmaniasis.³ Visceral leishmaniasis was a severe health burden during the early part of the 20th century, and it was a life saving drug for a large section of the population. Historically, it was the second drug developed against an infectious disease after Salversan (against Syphillis) and well before penicillin or sulfa drugs. It is still in use in many countries in a modified form.