Cholinesterases in human brain: the effect of cholinesterase inhibitors on Alzheimer's disease and related disorders

2006 ◽  
pp. 235-264 ◽  
Author(s):  
Ezio Giacobini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Cholinesterase Inhibitors

Drug Design of Inhibitors of Alzheimer’s Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of β-amino di-Carbonyl Derivatives

2019 ◽  
Vol 19 (8) ◽  
pp. 688-705
Author(s):  
Taibi Ben Hadda ◽  
Abdur Rauf ◽  
Hsaine Zgou ◽  
Fatma Sezer Senol ◽  
Ilkay Erdogan Orhan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Metal Accumulation ◽  
Microtiter Plate ◽  
Metal Chelation ◽  
Carbonyl Derivatives ◽  
Cholinesterase Inhibitory Activity ◽  
Inhibitory Potential

Background:Since deficit of acetylcholine has been evidenced in the Alzheimer’s disease (AD) patients, cholinesterase inhibitors are currently the most specified drug category for the remediation of AD.Method:In the present study, 16 compounds (1-16) with dicarbonyl skeletons have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 100 μg/mL. Since metal accumulation is related to AD, the compounds were also tested for their metal-chelation capacity.Results and Conclusion:All the investigated dicarbonyl compounds exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition towards BChE, being the most active. The highest metal-chelation capacity was observed with compound 8 (53.58 ± 2.06%). POM and DFT analyses are in good harmonization with experimental data.

Phenylalanine Metabolism is Dysregulated in Human Hippocampus with Alzheimer’s Disease Related Pathological Changes

2021 ◽  
pp. 1-14
Author(s):  
Pan Liu ◽  
Qian Yang ◽  
Ning Yu ◽  
Yan Cao ◽  
Xue Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Pathological Examination ◽  
Pathological Changes ◽  
Targeted Metabolomics ◽  
Phenylpyruvic Acid ◽  
Postmortem Human Brain ◽  
Metabolic Dysregulation ◽  
Phenylalanine Metabolism

Background: Alzheimer’s disease (AD) is one of the most challenging diseases causing an increasing burden worldwide. Although the neuropathologic diagnosis of AD has been established for many years, the metabolic changes in neuropathologic diagnosed AD samples have not been fully investigated. Objective: To elucidate the potential metabolism dysregulation in the postmortem human brain samples assessed by AD related pathological examination. Methods: We performed untargeted and targeted metabolomics in 44 postmortem human brain tissues. The metabolic differences in the hippocampus between AD group and control (NC) group were compared. Results: The results show that a pervasive metabolic dysregulation including phenylalanine metabolism, valine, leucine, and isoleucine biosynthesis, biotin metabolism, and purine metabolism are associated with AD pathology. Targeted metabolomics reveal that phenylalanine, phenylpyruvic acid, and N-acetyl-L-phenylalanine are upregulated in AD samples. In addition, the enzyme IL-4I1 catalyzing transformation from phenylalanine to phenylpyruvic acid is also upregulated in AD samples. Conclusion: There is a pervasive metabolic dysregulation in hippocampus with AD-related pathological changes. Our study suggests that the dysregulation of phenylalanine metabolism in hippocampus may be an important pathogenesis for AD pathology formation.

Pharmacotherapies for Alzheimer's disease: Beyond cholinesterase inhibitors

2012 ◽  
Vol 134 (1) ◽  
pp. 8-25 ◽  
Author(s):  
Haythum O. Tayeb ◽  
Hyun Duk Yang ◽  
Bruce H. Price ◽  
Frank I. Tarazi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors

scholarly journals Efficacy of SSRIs on cognition of Alzheimer's disease patients treated with cholinesterase inhibitors

2009 ◽  
Vol 22 (1) ◽  
pp. 114-119 ◽  
Author(s):  
Luca Rozzini ◽  
Barbara Vicini Chilovi ◽  
Marta Conti ◽  
Erik Bertoletti ◽  
Marina Zanetti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Mmse Score ◽  
Joint Effect ◽  
Negative Effects ◽  
Multidimensional Assessment ◽  
Degree Of Protection ◽  
Depressed Patients ◽  
The Mean

ABSTRACTBackground: This study examines the joint effect on cognition of selective serotonin re-uptake inhibitors (SSRIs) and cholinesterase inhibitors (AChEIs) in depressed patients affected by Alzheimer's disease (AD) living at home.Methods: The study was conducted in two different outpatient neurological clinics. 338 patients with probable AD were treated with ChEis (donepezil, rivastigmine and galantamine) as per the clinician's judgment and were observed for nine months. At study entry, participants underwent a multidimensional assessment evaluating cognitive, functional and psychobehavioral domains. All patients were evaluated at baseline, after one (T1), three (T2) and nine months (T3). Patients were grouped in three different categories (patients not depressed and not treated with SSRIs, patients depressed and treated with SSRIs, and patients depressed but not treated with SSRIs).Results: At baseline 182 were diagnosed as not depressed and not treated with SSRIs, 66 as depressed and treated with SSRIs, and 90 as depressed but not treated with SSRIs. The mean change in MMSE score from baseline to nine months showed that depressed patients not treated worsened in comparison with those not depressed and not treated with SSRIs (mean change −0.8 ± 2.3 vs 0.04 ± 2.9; p = 0.02) and patients depressed and treated with SSRI (mean change −0.8 ± 2.3 vs 0.1 ± 2.5; p = 0.03).Conclusions: In AD patients treated with AChEIs, SSRIs may exert some degree of protection against the negative effects of depression on cognition.

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