Acetylcholinesterase-Aβ Complexes Are More Toxic than Aβ Fibrils in Rat Hippocampus

Reyes, Ariel E.; Chacón, Marcelo A.; Dinamarca, Margarita C.; Cerpa, Waldo; Morgan, Carlos; Inestrosa, Nibaldo C.

doi:10.1016/s0002-9440(10)63774-1

Cited by 121 publications

(47 citation statements)

References 53 publications

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“…Experimental evidences illustrate that AChE accelerates aggregation of Ab peptide and formation of Ab-AChE complex at the synaptic region of hippocampus leading to DOI: 10.3109/13880209.2015.1017886 neuronal degeneration (Dinamarca et al, 2010;Reyes et al, 2004). Symptomatic treatment for AD involves potentiation of cholinergic activity through the inhibition of AChE (Rahman & Choudhary, 2001).…”

Section: Acetylcholinesterase and Butyrylcholinesterase Inhibitory Acmentioning

confidence: 99%

In vitroantioxidant and anti-cholinesterase activities ofRhizophora mucronata

Suganthy

Devi

2015

Pharmaceutical Biology

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Context: Rhizophora mucronata Lam. (Rhizophoraceae), commonly known as Asiatic mangrove, has been used traditionally among Asian countries as folk medicine. Objective: This study investigates the cholinesterase inhibitory potential and antioxidant activities of R. mucronata. Materials and method: Rhizophora mucronata leaves were successively extracted using solvents of varying polarity and a dosage of 100-500 mg/ml were used for each assay. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were assessed according to the method of Ellman. In vitro antioxidant activity was assessed using free radical scavenging, reducing power, and metal-chelating activity (duration -3 months). Total phenolic and flavonoid content were quantified spectrophotometrically. Compound characterization was done using column chromatography, NMR, FTIR, and LC-MS analysis. Results: Methanolic leaf extract (500 mg/ml) exhibited the highest inhibitory activity against AChE (92.73 ± 0.54%) and BuChE (98.98 ± 0.17%), with an IC 50 value of 59.31 ± 0.35 and 51.72 ± 0.33 mg/ml, respectively. Among the different solvent extracts, methanolic extract exhibited the highest antioxidant activity with an IC 50 value of 47.39 ± 0.43, 401.45 ± 18.52, 80.23 ± 0.70, and 316.47 ± 3.56 mg/ml for DPPH, hydroxyl, nitric oxide radical, and hydrogen peroxide, respectively. Total polyphenolic and flavonoid contents in methanolic extract were observed to be 598.13 ± 1.85 mg of gallic acid equivalent and 48.85 ± 0.70 mg of rutin equivalent/ mg of extract. Compound characterization illustrated (+)-catechin as the bioactive compound responsible for cholinesterase inhibitory and antioxidant activities. Conclusion: The presence of rich source of flavonoids, in particular catechin, might be responsible for its cholinesterase inhibitory and antioxidant activities.

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Section: Acetylcholinesterase and Butyrylcholinesterase Inhibitory Acmentioning

confidence: 99%

In vitroantioxidant and anti-cholinesterase activities ofRhizophora mucronata

Suganthy

Devi

2015

Pharmaceutical Biology

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“…[11] Because the adhesion function of AChE to Ab is located at the peripheral anionic site (PAS), [12] inhibitors that are able to bind both the catalytic active site (CAS) and PAS are of particular interest in AD, as they can simultaneously improve memory and slow the rate of amyloid degeneration.…”

Section: Introductionmentioning

confidence: 99%

“…Compounds containing a tether of six methylene units (5,8,11,16, and 21) showed shorter distances to PAS residues, indicating improved p-p stacking interactions. For instance, hybrid 11 (n = 6) showed better stabilizing interactions with PAS residues than its counterpart 10 (n = 5, Table 3).…”

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confidence: 99%

Tacrine–Melatonin Hybrids as Multifunctional Agents for Alzheimer's Disease, with Cholinergic, Antioxidant, and Neuroprotective Properties

et al. 2009

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Tacrine-melatonin hybrids were designed and synthesized as new multifunctional drug candidates for Alzheimer's disease. These compounds may simultaneously palliate intellectual deficits and protect the brain against both beta-amyloid (A beta) peptide and oxidative stress. They show improved cholinergic and antioxidant properties, and are more potent and selective inhibitors of human acetylcholinesterase (hAChE) than tacrine. They also capture free radicals better than melatonin. Molecular modeling studies show that these hybrids target both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. At sub-micromolar concentrations they efficiently displace the binding of propidium iodide from the PAS and could thus inhibit A beta peptide aggregation promoted by AChE. Moreover, they also inhibit A beta self-aggregation and display neuroprotective properties in a human neuroblastoma line against cell death induced by various toxic insults, such as A beta(25-35), H(2)O(2), and rotenone. Finally, they exhibit low toxicity and may be able to penetrate the central nervous system according to an in vitro parallel artificial membrane permeability assay for the blood-brain barrier (PAMPA-BBB).

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“…Aβ peptides deposition induces cholinergic denervation in AD [38]. Moreover, studies have shown that AChE could precipitate Aβ plaques deposition in the AD patients’ brain [39-41]. Somani et al [42] showed that chemical and physical stressors decrease choline acetyltransferase and AChE enzymes in the brain.…”

Section: Discussionmentioning

confidence: 99%

Exercise Improves Recognition Memory and Acetylcholinesterase Activity in the Beta Amyloid-Induced Rat Model of Alzheimer’s Disease

et al. 2018

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Objective: A correlation between physical exercise and cognitive improvement has been found in Alzheimer’s disease (AD). This study aimed to investigate the effects of aerobic and resistance exercise on the recognition memory and acetylcholinesterase (AChE) activity in beta amyloid (Aβ) model of AD in rat. Materials and Methods: Fifty male 8-week-old Wistar rats (250–280 g) were divided into 5 groups (n = 10 each) of control, sham surgery, Aβ-received sedentary, Aβ-received with aerobic exercise and Aβ-received with resistance exercise. AD was induced by intracerebroventricular injection of Aβ_25–35 peptide. The sham surgery group received normal saline using the same route and condition. Two groups of Aβ-received animals were trained by treadmill for aerobic exercise and by ladder for strength exercise for 8 weeks (4 days/week). Novel object recognition (NOR) task was used to assess recognitional memory in groups. AChE activity in the brain tissue was assessed using the Spectrophotometry method. Results: There was no significant difference in memory index and AChE activity between the sham surgery and control groups (p > 0.05). Also, impairment of NOR indices was seen in the Aβ-injected sedentary rats (p < 0.05). However, both aerobic and strength training improved the exploration index in this test (p < 0.05). Further, AChE activity increased in the Aβ-injected sedentary group but declined in the aerobic and resistance exercise groups (p < 0.01). Conclusion: Aerobic and resistance exercise could improve recognition memory and decrease AChE activity in Aβ-induced AD in rats. The decrease in AChE activity may be one of the mechanisms by which exercise improves cognition and memory in AD.

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Acetylcholinesterase-Aβ Complexes Are More Toxic than Aβ Fibrils in Rat Hippocampus

Cited by 121 publications

References 53 publications

In vitroantioxidant and anti-cholinesterase activities ofRhizophora mucronata

In vitroantioxidant and anti-cholinesterase activities ofRhizophora mucronata

Tacrine–Melatonin Hybrids as Multifunctional Agents for Alzheimer's Disease, with Cholinergic, Antioxidant, and Neuroprotective Properties

Exercise Improves Recognition Memory and Acetylcholinesterase Activity in the Beta Amyloid-Induced Rat Model of Alzheimer’s Disease

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