Verapamil attenuates scopolamine induced cognitive deficits by averting oxidative stress and mitochondrial injury - A potential therapeutic agent for Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial disorder where amyloid beta (Aβ) plaques, Ca dysregulation, excessive oxidative stress, mitochondrial dysfunction and synaptic loss operate synergistically to bring about cholinergic deficits and dementia. New therapeutic interventions are gaining prominence as the morbidity and mortality of AD increases exponentially every year. Treating AD with antihypertensive drugs is thought to be a promising intervention; however, its mechanism of action of ameliorating AD needs further investigation.

The significance of aryl acylamidase activity of acetylcholinesterase in osteoblast differentiation and mineralization.

Osteoblast differentiation is an essential event in the developmental process, which is favoured by the production of extra cellular matrix proteins and various enzymes including discrete ones like acetylcholinesterase (AChE). Despite the fact that AChE facilitates osteoblast differentiation, the significance of its catalytic functions [esterase and aryl acylamidase (AAA) activities] in the process is yet to be ascertained. In this context, SaOS-2 cell line was used in the present study to implicate the catalytic activities of AChE in process of osteoblast differentiation and mineralization.

Understanding the molecular mechanism of aryl acylamidase activity of acetylcholinesterase - An in silico study.

Acetylcholinesterase (AChE) exhibits two different activities, namely esterase and aryl acylamidase (AAA). Unlike esterase, AAA activity of AChE is inhibited by the active site inhibitors while remaining unaffected by the peripheral anionic site inhibitors. This differential inhibitory pattern of active and peripheral anionic site inhibitors on the AAA activity remains unanswered.

The allele frequency of T920C mutation in butyrylcholinesterase gene is high in an Indian population.

The genetic variants of butyrylcholinesterase (BChE) are the cause of concern in individuals experiencing prolonged apnea on administration of muscle relaxants. In an Indian community called Vysya, a variant (L307P; T920C) was associated with imperceptible plasma BChE. Since BChE has several pharmacological significances in humans, the identification of its variants having altered activity is very important.

A new role for the nonpathogenic nonsynonymous single-nucleotide polymorphisms of acetylcholinesterase in the treatment of Alzheimer's disease: a computational study.

Single-nucleotide polymorphisms (SNPs) are implicated in the complexity of understanding the genetics of diseases and their therapeutics. Here we have attempted to determine the impact of nonsynonymous SNPs (nsSNPs) on structure, dynamics, and ligand-binding properties of the human acetylcholinesterase (hAChE) protein, which has been targeted in the treatment of Alzheimer's disease. Of the reported 153 SNPs, 4 nsSNPs, namely, A415G, P104A, V302E, and Y119H, were prioritized to be functionally unfavorable by SIFT and PolyPhen algorithms.

Why calcium channel blockers could be an elite choice in the treatment of Alzheimer's disease: a comprehensive review of evidences.

The universality and vitality of calcium ions are implicit from its diverse physiological functions, from regulation of enzymes to synaptic plasticity and memory. However, overloading of these ions could result in life-threatening degenerative disorders. Calcium channels, which are involved in the transport of calcium ions, are targeted and blocked to prevent its overload, favoring vascular relaxation.

Altered mitochondrial biogenesis and its fusion gene expression is involved in the high-altitude adaptation of rat lung.

Intermittent hypobaric hypoxia-induced preconditioning (IHH-PC) of rat favored the adaption of lungs to severe HH conditions, possibly through stabilization of mitochondrial function. This is based on the data generated on regulatory coordination of nuclear DNA-encoded mitochondrial biogenesis; dynamics, and mitochondrial DNA (mtDNA)-encoded oxidative phosphorylation (mtOXPHOS) genes expression. At 16th day after start of IHH-PC (equivalent to 5000m, 6h/d, 2w of treatment), rats were exposed to severe HH stimulation at 9142m for 6h.

Adaptability to hypobaric hypoxia is facilitated through mitochondrial bioenergetics: an in vivo study.

Background And Purpose: High-altitude pulmonary oedema (HAPE) experienced under high-altitude conditions is attributed to mitochondrial redox distress. Hence, hypobaric hypoxia (HH)-induced alteration in expression of mitochondrial biogenesis and dynamics genes was determined in rat lung. Further, such alteration was correlated with expression of mitochondrial DNA (mtDNA)-encoded oxidative phosphorylation (mtOXPHOS) genes.

Interaction of metal chelators with different molecular forms of acetylcholinesterase and its significance in Alzheimer's disease treatment.

The peripheral anionic site (PAS) of acetylcholinesterase (AChE) is involved in amyloid beta (Aβ) peptides aggregation of Alzheimer's disease (AD). AChE exhibits an aryl acylamidase (AAA) activity along with the well known esterase activity. Numerous studies have reported the beneficiary effect of metal chelators in AD treatment.

An Indian butyrylcholinesterase variant L307P is not structurally stable: a molecular dynamics simulation study.

The human butyrylcholinesterase (BChE) activity is less than 1% in the serum of silent variant individuals of Vysya community in India. They are homozygous for a point mutation at codon 307 (CTT → CCT) resulting in the substitution of leucine 307 by proline. The reason for the disappearance of the protein in the serum has not been explicated till date.

High aryl acylamidase activity associated with cobra venom acetylcholinesterase: biological significance.

Investigation of the non-classical functions of cholinesterases (ChEs) has been the subject of interest in the past three decades. One of which is aryl acylamidase (AAA) activity associated with ChEs, but characterized in in vitro, as an enzyme, splitting the artificial substrate o-nitroacetanilide with unknown physiological function. In the present study, we have compared levels of AAA activity of AChE from different sources like goat brain, electric eel organ and from venoms of different snakes.

The aryl acylamidase activity is much more sensitive to Alzheimer drugs than the esterase activity of acetylcholinesterase in chicken embryonic brain.

The appearance of cholinergic trait often precedes synaptogenesis, indicating the involvement of cholinesterase proteins in nervous system development, particularly so acetylcholinesterase (AChE). In addition to AChE's acclaimed esterase activity, its lesser known non-cholinergic functions have gained much attention, because of AChE protein expression in areas other than cholinergic innervations; one such function could be exerted by its associated aryl acylamidase (AAA) activity. In this study, an attempt has been made in profiling esterase and AAA activities of AChE at different developmental stages of the chick embryo, e.

Evidence for presence of Zn+2-binding site in acetylcholinesterase.

The purified electric eel acetylcholinesterase (AChE) was able to bind to the Zn+2-chelate-Sepharose affinity column only on treatment with EDTA. However goat brain and cobra venom AChE were binding to the column even without EDTA treatment. But all these enzymes were eluted from Zn+2-chelate- Sepharose affinity column by EDTA.

Essential amino acids for the stability of human butyrylcholinesterase as predicted by CUPSAT server.

Although butyrylcholinesterase (BChE) is ubiquitous in the human system, its physiological function has often been questioned. Yet BChE has been the subject of active research since its discovery six decades ago. From an evolutionary view point, its stabilized existence even in absence of physiological function spared it from extinction.

Human serum cholinesterase from liver pathological samples exhibit highly elevated aryl acylamidase activity.

Background: Although aspartate aminotransferase (AST) and gamma-glutamyltransferase (gamma GT) enzymes are widely used as markers for liver disorders, the ubiquitous enzyme butyrylcholinesterase (BChE), synthesized in liver is also used as marker in the assessment of liver pathophysiology. This BChE enzyme in addition to its esterase activity has yet another enzymatic function designated as aryl acylamidase (AAA) activity. It is determined in in vitro based on the hydrolysis of the synthetic substrate o-nitroacetanilide.

Aryl acylamidase activity on acetylcholinesterase is high during early chicken brain development.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known to exhibit aryl acylamidase activities (here called AAA(AChe) and AAA(BChe), respectively), which have been suggested to be involved in developmental and pathological processes. We here have investigated the developmental profiles of both AAA(AChe) and AAA(BChe) activities along with their AChE and BChE activities from embryonic days E3 to hatching (E21) in Triton-extracted homogenates from chicken embryonic brains. AAA(AChe) follows continuously an increase that is typical for AChE expression itself, whereas AAA(BChe) was relatively high before E10 to then become negligible toward hatching.

Identification of serotonin-sensitive aryl acylamidase activity with cobra venom acetylcholinesterase.

Acetylcholinesterase purified from cobra (Naja naja) venom exhibits a serotonin-sensitive aryl acylamidase activity. Both acetylcholinesterase and aryl acylamidase activities co-eluted in column chromatographic procedures (Sephadex G-75 and Zinc-Sepharose), co-migrated on polyacrylamide gel electrophoresis, co-immunoprecipitated by anti-snake venom antibody and showed the same heat denaturation profile at 40 degrees C. Further, several potent acetylcholinesterase inhibitors at different concentrations inhibited the cholinesterase and aryl acylamidase activities to the same extent.