Other affiliations: West Bengal University of Technology
Bio: Soumalee Basu is an academic researcher from University of Calcutta. The author has contributed to research in topics: Amyloid precursor protein & Ectodomain. The author has an hindex of 8, co-authored 28 publications receiving 197 citations. Previous affiliations of Soumalee Basu include West Bengal University of Technology.
TL;DR: A multi-tier screening protocol combining ensemble docking to mine BACE1 inhibitor, as well as 2-D QSAR models for anti-amyloidogenic and antioxidant activities is designed and demonstrates the applicability of a novel multi-target screening procedure to mine multi-potent agents from natural origin for AD therapeutics.
TL;DR: The applicability of a multi-target screening strategy in AD therapeutics is demonstrated and the identified hit, narirutin, shows strong multi-potent activity.
TL;DR: An overview of the research carried out in discovering more efficient treatment against AD using Multi-Target-Directed Ligands based on the "one molecule multiple targets" paradigm that has been specifically adopted for the treatment of disorders with complex pathological mechanisms is provided.
Abstract: Alzheimer's Disease (AD) is a single major cause of dementia in middle to old age individuals involving several different etiopathological mechanisms that are yet to be properly characterized. Major invariant and characteristic features consist of the progressive cerebral deposition of the Amyloid β-protein (Aβ) and the neurofibrillary degeneration through Neurofibrillary Tangles (NFT) formed by hyperphosphorylation of the tau proteins in the regions of the brain that deal with memory and cognition. There are at least five subgroups of AD that can be identified by determining Cerebrospinal Fluid (CSF) levels of Aβ1-42, tau and ubiquitin. This multifactorial nature of the disease thus demands promising approaches for the development of rational disease-modifying drugs. A large number of agents have been discovered against individual targets but the success rate is very low and the number of compounds progressing to regulatory review is among the lowest found in any therapeutic area. A very promising modern approach solicits the design of Multi-Target-Directed Ligands (MTDLs) based on the "one molecule multiple targets" paradigm that has been specifically adopted for the treatment of disorders with complex pathological mechanisms. AD is one such disorder in which MTDL has found applicability. This review aims at providing an overview of the research carried out in discovering more efficient treatment against AD using MTDL, with a goal to ascertain safer drugs.
TL;DR: The conformational switching of BACE1 during APP recognition is explored using molecular dynamics simulation thereby suggesting the recognition to be a conformational selection process.
TL;DR: A hybrid structure-activity model containing both ligand based descriptors and energetic descriptors obtained from molecular docking based on a dataset of structurally diverse BACE1 inhibitors is designed that shows significant prediction ability judged by several statistical parameters.
Abstract: Mimicking receptor flexibility during receptor–ligand binding is a challenging task in computational drug design since it is associated with a large increase in the conformational search space. In the present study, we have devised an in silico design strategy incorporating receptor flexibility in virtual screening to identify potential lead compounds as inhibitors for flexible proteins. We have considered BACE1 (β-secretase), a key target protease from a therapeutic perspective for Alzheimer's disease, as the highly flexible receptor. The protein undergoes significant conformational transitions from open to closed form upon ligand binding, which makes it a difficult target for inhibitor design. We have designed a hybrid structure–activity model containing both ligand based descriptors and energetic descriptors obtained from molecular docking based on a dataset of structurally diverse BACE1 inhibitors. An ensemble of receptor conformations have been used in the docking study, further improving the prediction ability of the model. The designed model that shows significant prediction ability judged by several statistical parameters has been used to screen an in house developed 3-D structural library of 731 phytochemicals. 24 highly potent, novel BACE1 inhibitors with predicted activity (Ki) ≤ 50 nM have been identified. Detailed analysis reveals pharmacophoric features of these novel inhibitors required to inhibit BACE1.
01 Feb 1995
TL;DR: In this paper, the unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio using DFT, MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set.
Abstract: : The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg
01 Jan 2010
TL;DR: It is shown that prefibrillar aggregates of E22G (arctic) variant of the Abeta(1-42) peptide bind strongly to 1-anilinonaphthalene 8-sulfonate and that changes in this property correlate significantly with changes in its cytotoxicity.
Abstract: Oligomeric assemblies formed from a variety of disease-associated peptides and proteins have been strongly associated with toxicity in many neurodegenerative conditions, such as Alzheimer’s disease. The precise nature of the toxic agents, however, remains still to be established. We show that prefibrillar aggregates of E22G (arctic) variant of the Aβ1−42 peptide bind strongly to 1-anilinonaphthalene 8-sulfonate and that changes in this property correlate significantly with changes in its cytotoxicity. Moreover, we show that this phenomenon is common to other amyloid systems, such as wild-type Aβ1–42, the I59T variant of human lysozyme and an SH3 domain. These findings are consistent with a model in which the exposure of hydrophobic surfaces as a result of the aggregation of misfolded species is a crucial and common feature of these pathogenic species.
TL;DR: This overview was directed towards understanding the relationship of brain functions with dietary choices mainly by older humans, as they relate to dietary sufficiency or the association of antioxidants with neurodegenerative diseases such as dementia and Alzheimer’s disease.
Abstract: This overview was directed towards understanding the relationship of brain functions with dietary choices mainly by older humans. This included food color, flavor, and aroma, as they relate to dietary sufficiency or the association of antioxidants with neurodegenerative diseases such as dementia and Alzheimer’s disease. Impairment of olfactory and gustatory function in relation to these diseases was also explored. The role of functional foods was considered as a potential treatment of dementia and Alzheimer’s disease through inhibition of acetylcholinesterase as well as similar treatments based on herbs, spices and antioxidants therein. The importance of antioxidants for maintaining the physiological functions of liver, kidney, digestive system, and prevention of cardiovascular diseases and cancer has also been highlighted. Detailed discussion was focused on health promotion of the older person through the frequency and patterns of dietary intake, and a human ecology framework to estimate adverse risk factors for health. Finally, the role of the food industry, mass media, and apps were explored for today’s new older person generation.
Kerman Medical University1, RMIT University2, University of Medicine and Pharmacy of Craiova3, Duy Tan University4, University of Mauritius5, Durham University6, Çanakkale Onsekiz Mart University7, Tajik State Medical University8, University of Concepción9, University of Porto10, Hospital Authority11, Shahid Beheshti University of Medical Sciences and Health Services12
TL;DR: The mechanisms of action of some of the major herbal products with potential in the treatment of NDDs are reviewed according to their molecular targets, as well as their regional sources (Asia, America and Africa).
Abstract: Among the major neurodegenerative disorders (NDDs), Alzheimer’s disease (AD) and Parkinson’s disease (PD), are a huge socioeconomic burden. Over many centuries, people have sought a cure for NDDs from the natural herbals. Many medicinal plants and their secondary metabolites are reported with the ability to alleviate the symptoms of NDDs. The major mechanisms identified, through which phytochemicals exert their neuroprotective effects and potential maintenance of neurological health in ageing, include antioxidant, anti-inflammatory, antithrombotic, antiapoptotic, acetylcholinesterase and monoamine oxidase inhibition and neurotrophic activities. This article reviews the mechanisms of action of some of the major herbal products with potential in the treatment of NDDs according to their molecular targets, as well as their regional sources (Asia, America and Africa). A number of studies demonstrated the beneficial properties of plant extracts or their bioactive compounds against NDDs. Herbal products may potentially offer new treatment options for patients with NDDs, which is a cheaper and culturally suitable alternative to conventional therapies for millions of people in the world with age-related NDDs.
TL;DR: A review summarizes the recent studies on the role of BACE1 in synaptic functions as well as the views on Bace1 inhibition as an effective AD treatment.
Abstract: Alzheimer’s disease (AD), the most common cause of age-dependent dementia, is one of the most significant healthcare problems worldwide. Aggravating this situation, drugs that are currently US Food and Drug Administration (FDA)-approved for AD treatment do not prevent or delay disease progression. Therefore, developing effective therapies for AD patients is of critical urgency. Human genetic and clinical studies over the past three decades have indicated that abnormal generation or accumulation of amyloid-β (Aβ) peptides is a likely culprit in AD pathogenesis. Aβ is generated from amyloid precursor protein (APP) via proteolytic cleavage by β-site APP cleaving enzyme 1 (BACE1) (memapsin 2, β-secretase, Asp 2 protease) and γ-secretase. Mice deficient in BACE1 show abrogated production of Aβ. Therefore, pharmacological inhibition of BACE1 is being intensively pursued as a therapeutic approach to treat AD patients. Recent setbacks in clinical trials with BACE1 inhibitors have highlighted the critical importance of understanding how to properly inhibit BACE1 to treat AD patients. This review summarizes the recent studies on the role of BACE1 in synaptic functions as well as our views on BACE1 inhibition as an effective AD treatment.