Biochemistry and Pathophysiology of the Molecular Forms of Cholinesterases
TL;DR: The two types of ChE (generic abbreviation for any Cholinesterase) are readily distinguished not only by their substrate specificity but also by their response to selective inhibitors.
Abstract: Acetylcholinesterase (acetylcholine acetylhydrolase, AChE: EC 3.1.1.7) and butyrylcholinesterase (acylcholine acylhydrolase, BuChE: EC 3.1.1.8) both possess the capacity to hydrolyze choline esters, although the latter accepts a much wider variety of substrates. These two enzymes are found in a large number of excitable and nonexcitable tissues in most species, including humans (for review see Silver, 1974). The two types of ChE (generic abbreviation for any Cholinesterase) are readily distinguished not only by their substrate specificity but also by their response to selective inhibitors.
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TL;DR: In this article, the authors propose a method to identify the root cause of a problem.Abbreviations: [2]... ].., [3]
1,147 citations
TL;DR: The notions of diffuse transmission and of an ambient level of ACh in the CNS could also be of clinical relevance, in accounting for the production and nature of certain cholinergic deficits and the efficacy of substitution therapies.
433 citations
TL;DR: There is evidence that the most affected areas include the cortex, the entorhinal area, the hippocampus, the ventral striatum and the basal part of the forebrain, while other brain areas are less affected.
416 citations
TL;DR: Abnormal expression of AChE and BChE has been detected around the amyloid plaques and neurofibrillary tangles in the brains of patients with Alzheimer's disease and the presence of abnormal cholinesterase expression in the Alzheimer brain has implications for the pathogenesis of Alzheimer’s disease and for therapeutic strategies using choliersterase inhibitors.
174 citations
TL;DR: It has been suggested that the inhibition of these enzymes by the sterols and phlorotannins derived from marine brown algae could be a useful approach for the treatment of Alzheimer’s disease.
Abstract: As part of this study on the isolation of cholinesterase inhibitors from natural marine products, the bioactivity of the ethanolic extracts from 27 Korean seaweeds were screened using acetylcholinesterase (AChE) and butyrylcholine sterase (BChE) inhibitory assays. Ecklonia stolonifera exhibited promising inhibitory properties against both AChE and BChE. Bioassay-guided fractionation of the active n-hexane and ethyl acetate (EtOAc) soluble fractions, obtained from the ethanolic extract of E. stolonifera, resulted in the isolation of the sterols; fucosterol (1) and 24-hydroperoxy 24-vinylcholesterol (2), from the n-hexane fraction and the phlorotannins; phloroglucinol (3), ecks-tolonol (4), eckol (5), phlorofucofuroeckol-A (6), dieckol (7), triphlorethol-A (8), 2-phloroeckol (9) and 7-phloroeckol (10), from the EtOAc fraction. Of these, compounds 2, 9 and 10 were isolated from E. stolonifera for the first time. Compounds 4–7, 9 and 10 exhibited inhibitory potential against AChE, with 50% inhibition concentration (IC50) values of 42.66±8.48, 20.56±5,61, 4.89±2.28, 17.11±3.24, 38.13±4.95 and 21.11±4.16 μM, respectively; whereas, compounds 1, 2, 4 and 6 were found to be active against BChE, with IC50 values of 421.72±1.43, 176.46±2.51, 230.27±3.52 and 136.71±3.33 μM, respectively. It has been suggested that the inhibition of these enzymes by the sterols and phlorotannins derived from marine brown algae could be a useful approach for the treatment of Alzheimer’s disease.
148 citations
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TL;DR: A photometric method for determining acetylcholinesterase activity of tissue extracts, homogenates, cell suspensions, etc., has been described and Kinetic constants determined by this system for erythrocyte eholinesterases are presented.
23,015 citations
TL;DR: The use of avidin-biotin interaction in immunoenzymatic techniques provides a simple and sensitive method to localize antigens in formalin-fixed tissues.
Abstract: The use of avidin-biotin interaction in immunoenzymatic techniques provides a simple and sensitive method to localize antigens in formalin-fixed tissues. Among the several staining procedures available, the ABC method, which involves an application of biotin-labeled secondary antibody followed by the addition of avidin-biotin-peroxidase complex, gives a superior result when compared to the unlabeled antibody method. The availability of biotin-binding sites in the complex is created by the incubation of a relative excess of avidin with biotin-labeled peroxidase. During formation of the complex, avidin acts as a bridge between biotin-labeled peroxidase molecules; and biotin-labeled peroxidase molecules, which contains several biotin moieties, serve as a link between the avidin molecules. Consequently, a "lattice" complex containing several peroxidase molecules is likely formed. Binding of this complex to the biotin moieties associated with secondary antibody results in a high staining intensity.
13,480 citations
TL;DR: Demonstration of selective degeneration of neurons of the nucleus basalis of Meynert represents the first documentation of a loss of a transmitter-specific neuronal population in a major disorder of higher cortical function and points to a critical subcortical lesion in Alzheimer's patients.
Abstract: Recent evidence indicates that the nucleus basalis of Meynert, a distinct population of basal forebrain neurons, is a major source of cholinergic innervation of the cerebral cortex. Postmortem studies have previously demonstrated profound reduction in the presynaptic markers for cholinergic neurons in the cortex of patients with Alzheimer's disease and senile dementia of the Alzheimer's type. The results of this study show that neurons of the nucleus basalis of Meynert undergo a profound (greater than 75 percent) and selective degeneration in these patients and provide a pathological substrate of the cholinergic deficiency in their brains. Demonstration of selective degeneration of such neurons represents the first documentation of a loss of a transmitter-specific neuronal population in a major disorder of higher cortical function and, as such, points to a critical subcortical lesion in Alzheimer's patients.
3,544 citations
TL;DR: Colour is prooduced directly at the site of eoozyusuatic activity, facilitating estinsation of h.hue ooptinuuius imscusi)soti000s tinse; the l)necipitate is finselv grssusuulan, so) lhooot, eveos witis prolonged incusbosoh booms, needle-like deposits are not ob)served; instemuse cnol(on s
Abstract: 219 Ins thue exheussivelv ussed Koelle ;onsd Fniederuwald histociueuusbcal nuetisod Ion cisolinsestersose, amid its several ns(odificat ions (see Pearse, Histocheun istry, 2moded., p. 478, Little, Brown & Co., Bostons, 1960), thse tiuiociso)biose ester used as substrate is hydroiysed by cholimsestenosse, oond the liberated hhiocisohinue is captured h)\ Cu icns, pnecipitatirug sos colorless copper thiocisolbuse. The latter is convented to broot-nisis CuS by treatiuseust ot-iths yellow aissosuonununsu sulfide. Voonious steps irs thse nusethod hsovebee-mu criticized (Ion discussion see Pearse, ibid.). Lsorge useedle-like (‘rystals (occur l)articUbsonly sot sites oof isigh activity, at higher pH levels, oomsd wihis cvenlcomsg incusbatioru. Under somuse cmcuuuushsonuces, the crystals coons soppanently increase ins sizeby nsonu -euszvussat besoccnetions . (Mabnsgren sonod Syivo mu, J. Histocheun., 3: 441, 1955). Tise so(lvsonstages ccl thie presemutly described nssethsood sore: colour is prooduced directly at the site of eoozyusuatic activity, facilitating estinsation of h.hue ooptinuuius imscusi)soti000s tinse; the l)necipitate is finselv grssusuulan, so) lhooot, eveos witis prolonged incusbosoh booms, needle-like deposits are not ob)served; instemuse cnol(on sond contnsost coon conseqtiently be l)rodltlce-ib, somuch sites 0)1 low activity ussoone easily detected. TIse bsosis ol hbue issethod is that hisiochcdimseis l)elieved Its recluse-c ferricysonside to lerrocyoonide prefenenstisolly. The lootter coomiuhimues with Cu#{176} iomus to lonuss the iossolusb)le copper femnocyoonide (Hsotcheht’s l3rcowns). Tise Cti ions in the ussedium sore cocosuplexetl wit Is cit nsote too prevent fonisuation oof copper fennicysonside. Fcon best restults I huenose-I hucod is penlconsused as fooiioows: boloocks cof tissue sore fixed overmuiglut in coold 10#{176} Ionossooiims coomsh.ooirsbrsg 1% CaCI2 aoud are tbue-ms kept ins 0.88 11 sucrose-1’ guns arabic (Holt et al., .1. Biophys. Biocheno. (‘ytol., 7, 383, 1960). TIne blocks are wasised for five nusinutes in distilled ot-sote-r, blotted dry, sonuch sore quick-frozen in iso-
3,333 citations
3,312 citations