Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The evolution of senile plaques and the relationships among neuritic elements, extracellular deposits of the beta-amyloid protein (beta/A4), and vascular beta/A4 are poorly understood. Immunocytochemical methods were used to examine fixed-frozen prefrontal cortices of 14 rhesus monkeys (Macaca mulatta) (14 to 37 years of age) for the presence of abnormal fibers/neurites, alpha 1-antichymotrypsin (alpha-ACT), and beta/A4. Age-associated alterations included abnormal fibers/neurites, presence of beta/A4, and association of alpha-ACT with beta/A4 in plaques and blood vessels. Vascular amyloid was present only in the oldest monkeys. The topographic distribution of abnormal fibers/neurites was mapped with acetylcholinesterase (AChE) histochemistry, and deposits of amyloid were visualized with immunocytochemistry for beta/A4. beta/A4 often was associated with neurites, but many neurites lacked demonstrable beta/A4. Thus in aged monkeys, abnormal neurites may provide one type of focus for the accumulation of the amyloid precursor, which is subsequently abnormally processed to form beta/A4. Our data in rhesus monkeys suggest that fiber and neuritic abnormalities increase with age and that they may precede the majority of beta/A4 deposits; the initial stages of neurite formation and parenchymal amyloid deposits may be independent of the appearance of vascular amyloid; and these processes may be synergistic with advanced age.
 ...
PMID:Development of senile plaques. Relationships of neuronal abnormalities and amyloid deposits. 170 63

The histogenesis of alveolar soft part sarcoma (ASPS) has been investigated since its description. Twenty ASPS cases were analyzed for immunohistochemical content, with emphasis directed toward the paraganglial, Schwann cell, and muscle theories of histogenesis. In addition, the cases were examined for possible prognostic clinical features. The clinical characteristics of the patients were similar to those reported previously concerning average age (23 years); male:female ratio (1:1); and predominant primary site (lower extremity, nine cases). Despite a local recurrence rate of 20% and a metastatic rate of 68% (including four at presentation), the natural history was often indolent and relapse commonly occurred very late. The average follow-up period was 10.1 years. While the overall 5-year survival was 67%, only seven of 18 patients were alive without disease at last follow-up (1.7-32 years), and one patient died of tumor after a 28-year disease-free interval. Neither tumor size nor site appeared to affect prognosis. The tumors were analyzed immunohistochemically for neurofilament, S-100 protein, met-enkephalin, leu-enkephalin, acetylcholinesterase, alpha 1-antichymotrypsin, Factor VIII-related antigen, serotonin, lysozyme, neuron-specific enolase, myoglobin, cytokeratins, desmin, and vimentin. Except for weak vimentin immunoreactivity, no other antigenic expression was detected despite multiple repeated experiments with several antibodies. S-100 protein which is present in virtually all granular cell tumors was absent in the cases of ASPS. The lack of detectable expression of neurofilament, met-enkephalin and leu-enkephalin, and neuron-specific enolase is interpreted as evidence against the paraganglial theory of histogenesis. Similarly, the repeated absence of the muscle proteins, desmin and myoglobin, in contrast to a previous report, is interpreted as evidence against a myogenic origin.
 ...
PMID:Alveolar soft part sarcoma. A clinicopathologic and immunohistochemical study. 243 29

Eight liver biopsy specimens from five patients with PAS-negative intracisternal hyalin were investigated by immunofluorescence for: (1) immunoglobulins (Ig) G, A, M, D, E; (2) light chains (kappa and lambda); (3) complement components C1q, C4, C3c, C5, C9; (4) C1-inactivator; (5) C3-activator; (6) alpha 1-antitrypsin; (7) alpha 1-antichymotrypsin; (8) plasminogen; (9) fibrinogen; (10) fibrinogen breakdown products D and E; (11) fibronectin; (12) prealbumin; (13) albumin; (14) betalipoprotein; (15) apolipoprotein; (16) alpha 1- and alpha 2-glycoprotein; (17) cholinesterase; (18) ceruloplasmin; (19) haemopexin; (20) myoglobin; (21) placenta lactogen; (22) transferrin; (23) actin; (24) myosin; (25) cathepsin D; and (26) hepatitis B surface and core antigens (HBsAg and HBcAg). The globules reacted significantly with antisera against C3c (three patients), C4 (three patients), C3-activator (one patient) and fibrinogen (two patients). The cause of the protein accumulation is not clear. Serial studies indicate the possibility of a disturbance of protein secretion and an as yet unidentified immune complex disorder.
 ...
PMID:Immunohistological investigations of PAS-negative globular intracisternal hyalin in human liver biopsy specimens. 285 88

Although serum cholinesterase (CHE) is elevated in some hyperlipidaemic subjects, the relationship between serum CHE and lipids in normolipidaemic subjects is scanty. Furthermore, serum CHE is reduced in conditions in which there is an acute phase response. Serum CHE activity was measured in 46 normal individuals (22 males and 24 females). There was no significant difference between the activity of serum CHE in males or females being 6.2 +/- 1.8 U1(-1) vs. 6.4 +/- 1.5 U1(-1) respectively (mean +/- SD). There was, however, a significant correlation between serum CHE and subject age (Spearman rho 0.35, p < 0.05). There was also a significant correlation between serum CHE and serum nonfasting triglyceride concentration (rho 0.34, p < 0.05) and also apolipoprotein B (rho 0.38, p < 0.05) but not serum cholesterol or HDL-cholesterol. Five serum acute phase proteins were measured namely serum alpha-1 antichymotrypsin (ACT), alpha-1-acid-glycoprotein (AGP), alpha-2-macroglobulin (AMG), C-reactive protein (CRP), haptoglobin (HAP). Only serum AGP showed a significant negative correlation with serum CHE (rho - 0.43, p < 0.02).
 ...
PMID:Serum lipids, acute phase proteins and serum cholinesterase in normal subjects. 753 45

The genetic associations with the pathological features of AD are diverse: A rapidly growing number of mutations in presenilin 1 and 2 on chromosomes 14 and 1, respectively, are found in many early-onset FAD patients (Lendon et al., 1997). In addition, beta PP mutations are found in a small percentage of early-onset FAD kindreds. The apoE4 allele on chromosome 19 is associated with the presence of the most common form of AD, sporadic AD (Wisniewski & Frangione, 1992; Namba et al., 1991). However, it is clear that other proteins are also involved in the pathogenesis of AD, since some early-onset FAD kindreds do not have linkage to PS1, PS2, apoE, or beta PP, while at least 50% of late-onset AD is unrelated to apoE. Other proteins which have been implicated in the formation of senile plaques, but so far are not known to have any genetic linkage to AD, include proteoglycans (Snow et al., 1987), apoA1 (Wisniewski et al., 1995a), alpha 1-antichymotrypsin (Abraham et al., 1988), HB-GAM (Wisniewski et al., 1996a), complement components (McGeer & Rogers, 1992), acetylcholinesterase (Friede, 1965), and NAC (Ueda et al., 1993). Which of these proteins will be the most important for the etiology of the most common form of AD, late-onset sporadic AD, remains an open question. Three of the genes which are now known to be linked to AD, including PS1, beta PP, and apoE, have been established immunohistochemically and biochemically to be components of senile plaques (see Fig. 1). This raises at least two possibilities: either each of these proteins is part of one pathway with A beta-related amyloid formation as a final causative pathogenic event or amyloid deposition in AD is a reactive process related to dysfunction of a number of different CNS proteins. Whether or not amyloid formation is directly causative in the pathogenesis of AD, current data suggest that new therapeutic approaches which may inhibit the aggregation and/or the conformational change of sA beta to A beta fibrils (Soto et al., 1996) have the greatest likelihood to make a significant impact on controlling amyloid accumulation in AD.
 ...
PMID:Biology of A beta amyloid in Alzheimer's disease. 944 Jan 20

Alzheimer's disease (AD) is a genetically complex disorder associated with multiple genetic defects either mutational or of susceptibility. Current AD genetics does not explain in full the etiopathogenesis of AD, suggesting that environmental factors and/or epigenetic phenomena may also contribute to AD pathology and phenotypic expression of dementia. The genomics of AD is still in its infancy, but is helping us to understand novel aspects of the disease including genetic epidemiology, multifactorial risk factors, pathogenic mechanisms associated with genetic networks and genetically-regulated metabolic cascades. AD genomics is also fostering new strategies in pharmacogenomic research and prevention. Functional genomics, proteomics, pharmacogenomics, high-throughput methods, combinatorial chemistry and modern bioinformatics will greatly contribute to accelerating drug development for AD and other complex disorders. The multifactorial genetic dysfunction in AD includes mutational loci (APP, PS1, PS2) and diverse susceptibility loci (APOE, A2M, AACT, LRP1, IL1A, TNF, ACE, BACE, BCHE, CST3, MTHFR, GSK3B, NOS3) distributed across the human genome, probably converging in common pathogenic mechanisms that lead to premature neuronal death. Genomic associations integrate polygenic matrix models to elucidate the genomic organization of AD in comparison to the control population. Using APOE-related monogenic models it has been demonstrated that the therapeutic response to drugs (e.g., cholinesterase inhibitors, non-cholinergic compounds) in AD is genotype-specific. A multifactorial therapy combining three different drugs yielded positive results during 6-12 months in approximately 60% of the patients. With this therapeutic strategy, APOE-4/4 carriers were the worst responders and patients with the APOE-3/4 genotype were the best responders. Other polymorphic variants (PS1, PS2) also influence the therapeutic response to different drugs in AD patients, suggesting that the final pharmacological outcome is the result of multiple genomic interactions, including AD-related genes and genes associated with drug metabolism, disposition, and elimination. The pharmacogenomics of AD may contribute in the future to optimise drug development and therapeutics, increasing efficacy and safety, and reducing side-effects and unnecessary costs.
 ...
PMID:Pharmacogenomics for the treatment of dementia. 1245 80

The antichymotrypsin, antitrypsin, and anticholinesterase efficiencies of four homologous series of organophosphorus inhibitors are compared: O-ethyl-S-(n-alkyl)methylthiophosphonates, O-(n-alkyl)-S-(n-butyl)methylthiophosphonates, O-(n-alkyl)-S-beta-(ethylmercaptoethylene)methylthiophosphonates, and their methylsulfomethylates. As sources of a-chymotrypsin and trypsin, commercial compounds of Worthington Biochemical Corporation and Leningrad Myasokombinat were tested. Bimolecular constant of the reaction rate was used as the measure of antienzyme efficiency. In all cases, the antichymotrypsin efficiency was lower, while the antitrypsin--essentially higher than the anticholinesterase activity of the studied inhibitors. These differences were found to much depend both on the inhibitor structure and on nature of the cholinesterase compounds.
 ...
PMID:[Comparative analysis of sensitivity of proteases (chymotrypsin and trypsin) and cholinesterases of different origin to some organophosphorus inhibitors]. 1956 52