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A robust preclinical disease model is a primary requirement to understand the underlying mechanisms, signaling pathways, and drug screening for human diseases. Although various preclinical models are available for several diseases, clinical models for Alzheimer’s disease (AD) remain underdeveloped and inaccurate. The pathophysiology of AD mainly includes the presence of amyloid plaques and neurofibrillary tangles (NFT). Furthermore, neuroinflammation and free radical generation also contribute to AD. Currently, there is a wide gap in scientific approaches to preventing AD progression. Most of the available drugs are limited to symptomatic relief and improve deteriorating cognitive functions. To mimic the pathogenesis of human AD, animal models like 3XTg-AD and 5XFAD are the primarily used mice models in AD therapeutics. Animal models for AD include intracerebroventricular-streptozotocin (ICV-STZ), amyloid beta-induced, colchicine-induced, etc., focusing on parameters such as cognitive decline and dementia. Unfortunately, the translational rate of the potential drug candidates in clinical trials is poor due to limitations in imitating human AD pathology in animal models. Therefore, the available preclinical models possess a gap in AD modeling. This paper presents an outline that critically assesses the applicability and limitations of the current approaches in disease modeling for AD. Also, we attempted to provide key suggestions for the best-fit model to evaluate potential therapies, which might improve therapy translation from preclinical studies to patients with AD.

Aim: A breakthrough in modern medicine, in terms of treatment of Alzheimer’s disease, is yet to be seen, as the scene is currently plagued with numerous clinical trial failures. Here, we are exploring multifunctional hybrid sulfonamides for their anti-Alzheimer activity due to the complex nature of the disease. Results & methodology: Compound 41 showed significant inhibition of MMP-2 (IC50: 18.24 ± 1.62 nM), AChE (IC50: 4.28 ± 0.15 μM) and BuChE (IC50: 1.32 ± 0.02 μM). It also exhibited a metal-chelating property, as validated by an in vitro metal-induced Aβ aggregation assay using confocal fluorescence imaging. Whereas, MTT and DPPH assays revealed it to be nontoxic and neuroprotective with substantial antioxidant property. Conclusion: The present study puts forth potent yet nontoxic lead molecules, which foray into the field of multitargeted agents for the treatment of Alzheimer’s disease.

Background: Hydroxamic acids are a major class of organic compounds. They have a wide variety of pharmacological actions in targeting cancers, cardiovascular diseases, HIV, Alzheimer's disease, Malaria, Allergic diseases. Objective: The present review focuses on the chemistry of conventional and non-conventional routes for the synthesis of hydroxamic acids reported till date. Conclusion: The hydroxamic acids are conventionally synthesized via carboxylic acid and their acid chloride derivatives. However, some other functional groups i.e. aldehyde, amine, amide and alcohol can also be converted to hydroxamate with ease. The solid phase synthesis techniques are also gaining importance for the synthesis of hydroxamic acids and these pathways have opened a wide arena for the synthesis of diverse and complex hydroxamic acids.

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Background: Alzheimer’s Disease (AD), a multifaceted disorder, involves complex pathophysiology and plethora of protein-protein interactions. Thus such interactions can be exploited to develop anti-AD drugs. Objective: The interaction of dynamin-related protein 1, cellular prion protein, phosphoprotein phosphatase 2A and Mint 2 with amyloid β, etc., studied recently, may have critical role in progression of the disease. Our objective has been to review such studies and their implications in design and development of drugs against the Alzheimer’s disease. Methods: Such studies have been reviewed and critically assessed. Results: Review has led to show how such studies are useful to develop anti-AD drugs. Conclusion: There are several PPIs which are current topics of research including Drp1, Aβ interactions with various targets including PrPC, Fyn kinase, NMDAR and mGluR5 and interaction of Mint2 with PDZ domain, etc., and thus have potential role in neurodegeneration and AD. Finally, the multi-targeted approach in AD may be fruitful and opens a new vista for identification and targeting of PPIs in various cellular pathways to find a cure for the disease.

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Carboxylic and dicarboxylic acids (glycolic, oxalic, malonic and succinic) have been extracted with tetrahydrofuran (THF) and H2O from large synthetic MgO crystals, crushed to a medium fine powder. The extracts were characterized by infrared spectroscopy and 1H-NMR. The THF extracts were derivatized with tert-butyldimethylsilyl (t-BDMS) for GC-MS analysis. A single crystal separated from the extract was used for an x-ray structure analysis, giving the monoclinic unit cell, space group P21/c with ao = 5.543 A, bo = 8.845 A, co = 5.086 A, and beta = 91.9 degrees, consistent with beta-succinic acid, HOOC(CH2)COOH. The amount of extracted acids is estimated to be of the order of 0.1 to 0.5 mg g-1 MgO. The MgO crystals from which these organic acids were extracted grew from the 2860 degrees C hot melt, saturated with CO/CO2 and H2O, thereby incorporating small amounts of the gaseous components to form a solid solution (ss) with MgO. Upon cooling, the ss becomes supersaturated, causing solute carbon and other solute species to segregate not only to the surface but also internally, to dislocations and subgrain boundaries. The organic acids extracted from the MgO crystals after crushing appear to derive from these segregated solutes that formed C-C, C-H and C-O bonds along dislocations and other defects in the MgO structure, leading to entities that can generically be described as (HxCyOz)n-. The processes underlying the formation of these precursors are fundamental in nature and expected to be operational in any minerals, preferentially those with dense structures, that crystallized in H2O-CO2-laden environments. This opens the possibility that common magmatic and metamorphic rocks when weathering at the surface of a tectonically active planet like Earth may be an important source of abiogenically formed complex organic compounds.