Enhanced Butyrylcholinesterase Activity may be the Common Link in Triggering Low-Grade Systemic Inflammation and Decrease in Cognitive Function in Diabetes Mellitus and Alzheimers disease

Rao, Allam Appa; Reddy, C. Siva; Sridhar, G. R.; Akula, Annapurna; Thota, Hanuman; Prameela, M.; Suresh, K; Prasannalaxmi, S.; Das, Undurti N.

doi:10.2174/157340108785133310

Cited by 8 publications

(7 citation statements)

References 23 publications

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“…This is similar to the hypothesis based on bioinformatics analysis that the enzyme butyrylcholinesterase could be related to the pathogenesis of Alzheimer's disease and type 2 diabetes mellitus [37]. The hypothesis was followed up by an animal study in which streptozotocin-induced diabetes in albino Wistar rats showed a decline in cognitive function and an increased serum butyrylcholinesterase [38]. A series of other studies have suggested that it could be one of the mediators between type 2 diabetes mellitus and Alzheimer's disease [39].…”

supporting

confidence: 74%

Diabetes and data in many forms

Sridhar¹

2016

Int J Diabetes Dev Ctries

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supporting

confidence: 74%

Diabetes and data in many forms

Sridhar¹

2016

Int J Diabetes Dev Ctries

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“…BuChE selectivity appears to be important not only in AD but also in regard to inflammation, oxidative stress, and lipid metabolism [ 54 ]. For instance, it has been shown that streptozotocin-induced diabetic animals had dyslipidemia, increased plasma lipid peroxide content, decreased circulating plasma superoxide dismutase activity, and increased BuChE level [ 55 ]. In addition, elevated BuChE activity can lead to decreased ACh levels, thereby resulting in low-grade systemic inflammation [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, it has been shown that streptozotocin-induced diabetic animals had dyslipidemia, increased plasma lipid peroxide content, decreased circulating plasma superoxide dismutase activity, and increased BuChE level [ 55 ]. In addition, elevated BuChE activity can lead to decreased ACh levels, thereby resulting in low-grade systemic inflammation [ 55 ]. Furthermore, there are also some studies that suggest that selective, reversible inhibition of brain BuChE may serve as a treatment for AD, improving cognition and modulating neuropathological AD markers such as inflammation [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

Markowicz-Piasecka

Sikora

Mateusiak

et al. 2017

Oxidative Medicine and Cellular Longevity

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The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM) may predispose to Alzheimer's disease (AD). The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress. The diabetic state also contributes to increased acetylcholinesterase (AChE) activity, which is one of the factors leading to neurodegeneration in AD. The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE) and establish the type of inhibition. Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 μmol/mL, mixed type of inhibition) and seemed to be selective towards AChE since it presented low anti-BuChE activity. The tested metformin prodrugs inhibited cholinesterases (ChE) at nanomolar range and thus were more active than metformin or phenformin. The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC50 = 890 nmol/mL, noncompetitive inhibition) and BuChE (IC50 = 28 nmol/mL, mixed type inhibition), while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC50 = 184 nmol/mL). Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE. In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future.

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“…Elevated BChE could lead to decreased acetylcholine levels and anti-inflammatory molecule, thereby resulting in a low-grade systemic inflammation. That may account for the decline in cognitive function [33]. Furthermore, individuals carrying the apolipoprotein E (APOE) epsilon four allele, and particularly those with both APOE and BChE K-variant alleles, have the fastest cognitive decline among subjects with amnestic mild cognitive impairment, mild AD and the slowest decline in more advanced stages of the illness [34][35][36].…”

Section: Discussionmentioning

confidence: 99%

Abdominal Obesity Associated with Elevated Serum Butyrylcholinesterase Activity, Insulin Resistance and Reduced High Density Lipoprotein-Cholesterol Levels

et al. 2014

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Abdominal obesity (AO) has a strong correlation with cardiovascular disease and has been linked to Alzheimer's disease and type 2 diabetes. We investigated the association between AO and elevated serum butyrylcholinesterase (BChE) activity, insulin resistance and the serum lipid profile, including triglyceride (TG), HDLcholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels in AO and non-AO women subjects. A total of 500 AO subjects (age 49.1 ± 10.5 years), and 142 non-AO women subjects (age 49.9 ± 11.9 years) were enrolled for the general biochemistry tests, serum BChE, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Body mass index, waist circumference, Blood pressure (BP), plasma glucose (Glu), triglyceride (TG), BChE, insulin, HOMA-IR were significantly higher and HDL-C levels were significantly lower in AO subjects (p \ 0.05). Waist circumference was significantly correlated with BP, Glu, TG, BChE, insulin and HOMA-IR in AO subjects. Multiple logistic regression demonstrated that AO was associated with elevated BChE, HOMA-IR, hypertension and reduced HDL-C after adjusting for these variables. AO is associated with elevated BChE, insulin resistance, HT and reduced HDL-C. These may predict the development of type 2 diabetes mellitus and may be associated with cognitive disorder in the future, both are mediated through insulin resistance.

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Enhanced Butyrylcholinesterase Activity may be the Common Link in Triggering Low-Grade Systemic Inflammation and Decrease in Cognitive Function in Diabetes Mellitus and Alzheimers disease

Cited by 8 publications

References 23 publications

Diabetes and data in many forms

Diabetes and data in many forms

Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

Abdominal Obesity Associated with Elevated Serum Butyrylcholinesterase Activity, Insulin Resistance and Reduced High Density Lipoprotein-Cholesterol Levels

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