As a \"silent threat,\" Alzheimer\'s disease (AD) is quickly rising to the top of the list of costly and troublesome diseases facing humanity. It is growing to be one of the most troublesome and expensive conditions, with annual health care costs higher than those of cancer and comparable to those of cardiovascular disorders. One of the main pathogenic characteristics of AD is the deficiency of the neurotransmitter acetylcholine (ACh) which plays a vital role in memory, learning, and attention. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) play a crucial role in hydrolyzing ACh. Consequently, a frequent therapy approach for AD is the suppression of AChE and BChE to improve cholinergic neurotransmission and reduce cognitive symptoms. The accumulation of amyloid plaques (Aβ) is a primary factor contributing to neurodegenerative diseases, particularly AD. Glycogen synthase kinase-3β (GSK3-β) is regarded as a pivotal player in the pathophysiology of AD since dysregulation of this kinase affects all major hallmarks of the disease, such as tau phosphorylation, Aβ aggregation, memory, neurogenesis, and synaptic function. One of the most challenging and risky issues in modern medicinal chemistry is the urgent and ongoing need for the study and development of effective therapeutic candidates for the treatment of AD. A significant class of heterocyclic molecules that can target the complex and multifactorial pathogenesis of AD are fused thiophene derivatives. The goal of the current review is to demonstrate the advancements made in fused thiophene derivatives\' anti-AD activity. It also covers their mechanisms of action and studies of the structure-activity relationships in addition to the compilation of significant synthetic routes for fused thiophene derivatives with anti-AD potential. This review is intended to stimulate new ideas in the search for more rationale designs of derivatives based on fused thiophene, hoping to be more potent in treating AD.

Prolonged and excessive use of chlorpyrifos (CPS) has caused severe pollution, particularly in crops, vegetables, fruits, and water sources. As a result, CPS is detected in various food and water samples using conventional methods. However, its applications are limited due to size, portability, cost, etc. In this regard, electrochemical sensors are preferred for CPS detection due to their high sensitivity, reliability, rapid, on-site detection, and user-friendly. Notably, graphene-based electrochemical sensors have gained more attention due to their unique physiochemical and electrochemical properties. It shows high sensitivity, selectivity, and quick response because of its high surface area and high conductivity. In this review, we have discussed an overview of three graphene-based different functional electrochemical sensors such as electroanalytical sensors, bio-electrochemical sensors, and photoelectrochemical sensors used to detect CPS in food and water samples. Furthermore, the fabrication and operation of these electrochemical sensors using various materials (low band gap material, nanomaterials, enzymes, antibodies, DNA, aptamers, and so on) and electrochemical techniques (CV, DPV, EIS, SWV etc.) are discussed. The study found that the electrical signal was reduced with increasing CPS concentration. This is due to the blocking of active sites, reduced redox reaction, impedance, irreversible reactions, etc. In addition, acetylcholinesterase-coupled sensors are more sensitive and stable than others. Also, it can be further improved by fabricating with low band gap nanomaterials. Despite their advantages, these sensors have significant drawbacks, such as low reusability, repeatability, stability, and high cost. Therefore, further research is required to overcome such limitations.

Alzheimer\'s disease (AD) is a chronic and irreversible neurodegenerative disorder with progressive dementia and cognitive impairment. AD poses severe health challenge in elderly people and become one of the leading causes of death worldwide. It possesses complex pathophysiology with several hypotheses (cholinergic hypothesis, amyloid hypothesis, tau hypothesis, oxidative stress, mitochondrial dysfunction etc.). Several attempts have been made for the management of multifactorial AD. Acetylcholinesterase is the only target has been widely explored in the management of AD to the date. The current review set forth the chalcone based natural, semi-synthetic and synthetic compounds in the search of potential anti-Alzheimer\'s agents. The main highlights of current review emphasizes on chalcone target different enzymes and pathways like Acetylcholinesterase, β-secretase (BACE1), tau proteins, MAO, free radicals, Advanced glycation end Products (AGEs) etc. and their structure activity relationships contributing in the inhibition of above mentioned various targets of AD.

Alzheimer\'s disease (AD) is a chronic neurodegenerative disease. It is clinically characterized by memory loss and intellectual decrease, among other neurological deficits. The etiology of AD is not completely understood but includes amyloid plaques and intracellular helical filaments as well as neurofibrillary tangles with hyperphosphorylated tau protein. AD is also associated with alterations in amyloid processing genes, such as PSEN1 or PSEN2 and APP. The modulation immune system, cholesterol metabolism, and synaptic vesicle endocytosis have all been shown to remediate AD. In this review, enzymes such as AChE, BuChE, β-secretase, γ-secretase, MAO, and RAGE are discussed as potential targets for AD treatment. The aim of this review was to addresses the molecular mechanisms as well as various genetic factors in AD etiology. The use of natural compounds against these targets might be beneficial for the management of AD.

In this review, we discuss the genetic etiologies of Alzheimer\'s disease (AD). Furthermore, we review genetic links to protein signaling pathways as novel pharmacological targets to treat AD. Moreover, we also discuss the clumps of AD-m ediated genes according to their single nucleotide polymorphism mutations. Rigorous data mining approaches justified the significant role of genes in AD prevalence. Pedigree analysis and twin studies suggest that genetic components are part of the etiology, rather than only being risk factors for AD. The first autosomal dominant mutation in the amyloid precursor protein (APP) gene was described in 1991. Later, AD was also associated with mutated early-onset (presenilin 1/2, PSEN1/2 and APP) and late-onset (apolipoprotein E, ApoE) genes. Genome-wide association and linkage analysis studies with identified multiple genomic areas have implications for the treatment of AD. We conclude this review with future directions and clinical implications of genetic research in AD.

Sarin (GB, O-isopropyl methylphosphonofluoridate) is a potent organophosphorus (OP) nerve agent that inhibits acetylcholinesterase (AChE) irreversibly. The subsequent build-up of acetylcholine (ACh) in the central nervous system (CNS) provokes seizures and, at sufficient doses, centrally-mediated respiratory arrest. Accumulation of ACh at peripheral autonomic synapses leads to peripheral signs of intoxication and overstimulation of the muscarinic and nicotinic receptors, which is described as \"cholinergic crisis\" (i.e. diarrhea, sweating, salivation, miosis, bronchoconstriction). Exposure to high doses of sarin can result in tremors, seizures, and hypothermia. More seriously, build-up of ACh at neuromuscular junctions also can cause paralysis and ultimately peripherally-mediated respiratory arrest which can lead to death via respiratory failure. In addition to its primary action on the cholinergic system, sarin possesses other indirect effects. These involve the activation of several neurotransmitters including gamma-amino-butyric acid (GABA) and the alteration of other signaling systems such as ion channels, cell adhesion molecules, and inflammatory regulators. Sarin exposure is associated with symptoms of organophosphate-induced delayed neurotoxicity (OPIDN) and organophosphate-induced chronic neurotoxicity (OPICN). Moreover, sarin has been involved in toxic and immunotoxic effects as well as organophosphate-induced endocrine disruption (OPIED). The standard treatment for sarin-like nerve agent exposure is post-exposure injection of atropine, a muscarinic receptor antagonist, accompanied by an oxime, an AChE reactivator, and diazepam.