Acetylcholinesterase Interaction with Alzheimer Amyloid β

Inestrosa, Nibaldo C.; Sagal, Juan Paulo; Colombres, Marcela

doi:10.1007/0-387-23226-5_15

Cited by 89 publications

(77 citation statements)

References 51 publications

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“…In vitro studies showed that AChE accelerates the assembly of the Aβ peptide into amyloid fibrils [80][81][82][83] through a specific structural motif [84]. On the other hand, in vivo studies demonstrated that increased AChE expression is able to induce plaque formation [85,86] (for reviews, see [87,88]). AChE is used as an indicator when analyzing human IBM biopsies in order to establish whether the neuromuscular junction has been formed [24], but it has not been described as forming part of the inclusions in the vacuolated muscle fibers.…”

Section: Inclusion Body Myositismentioning

confidence: 99%

Inclusion Body Myositis: A View from the Caenorhabditis elegans Muscle

Rebolledo¹,

Minniti²,

Grez³

et al. 2008

Mol Neurobiol

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Inclusion body myositis (IBM) is the most common myopathy in people over 50 years of age. It involves an inflammatory process that, paradoxically, does not respond to anti-inflammatory drugs. A key feature of IBM is the presence of amyloid-beta-peptide aggregates called amyloid deposits, which are also characteristic of Alzheimer's disease. The use of animals that mimic at least some characteristics of a disease has become very important in the quest to elucidate the molecular mechanisms underlying this and other pathogeneses. Although there are some transgenic mouse strains that recreate some aspects of IBM, in this review, we hypothesize that the great degree of similarity between nematode and human genes known to be involved in IBM as well as the considerable conservation of biological mechanisms across species is an important feature that must be taken into consideration when deciding on the use of this nematode as a model. Straightforward laboratory techniques (culture, transformation, gene knockdown, genetic screenings, etc.) as well as anatomical, physiological, and behavioral characteristics add to the value of this model. In the present work, we review evidence that supports the use of Caenorhabditis elegans as a biological model for IBM.

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Section: Inclusion Body Myositismentioning

confidence: 99%

Inclusion Body Myositis: A View from the Caenorhabditis elegans Muscle

Rebolledo¹,

Minniti²,

Grez³

et al. 2008

Mol Neurobiol

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“…For example, acetylcholinesterase induces Aβ formation in AD. Cholinesterase inhibitors, in particular, help to reduce Aβ aggregation and slow the process of neurodegeneration (74–75). Based on the findings in the Bana study, the clinical effectiveness of cholinesterase inhibitors may be enhanced or prolonged by co-administration of bi-functionalized mApoE-PA-LIP.…”

Section: The Roles Of Various Lipid Classes In Disease Pathophysiologiesmentioning

confidence: 99%

Lipidomics in translational research and the clinical significance of lipid-based biomarkers

Stephenson

Hoeferlin

Chalfant

2017

Translational Research

103

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Lipidomics is a rapidly developing field of study that focuses on the identification and quantitation of various lipid species in the lipidome. Lipidomics has now emerged in the forefront of scientific research due to the importance of lipids in metabolism, cancer, and disease. Using both targeted and untargeted mass spectrometry as a tool for analysis, progress in the field has rapidly progressed in the last decade. Having the ability to assess these small molecules in vivo has led to better understanding of several lipid-driven mechanisms and the identification of lipid-based biomarkers in neurodegenerative disease, cancer, sepsis, wound healing, and pre-eclampsia. Biomarker identification and mechanistic understanding of specific lipid pathways linked to a disease pathologies can form the foundation in the development of novel therapeutics in hopes of curing human disease.

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“…Yellow powder, yield: 48%, mp 55-56 ( (27 (E)-3-(4-phenoxyphenyl)-N-(6-((1,2,3,4-tetrahydroacridin-9-yl)amino)hexyl)acrylamide (35). Yellow powder, yield: 28%, mp 47-49 C. …”

Section: Chemistrymentioning

confidence: 99%

“…Such substitution was favourable for AChE inhibition, the two compounds exhibited a good selectivity on AChE. We next introduced benzyloxy group at the para-position of the cinnamic acid moiety 35 . Compared to 12, the activities of the three compounds on AChE were remarkably reduced, while the BuChE activities were maintained.…”

Section: Ches Inhibitory Activity and Sar Analysismentioning

confidence: 99%

“…Catalytic triads in CAS of hAChE and hBuChE consist of conserved amino acids: Ser203, His447, Glu334 in hAChE and Ser198, His438, Glu325 in hBuChE 34 . PAS of hAChE is proved to be closely related to both hydrolysis of ACh and neurotoxic cascade of AD through AChE-induced b-amyloid (Ab) aggregation 35 . As a result, designing MTDLs targeting both CAS and PAS attracts the attentions of medicinal chemists throughout the world.…”

Section: Introductionmentioning

confidence: 99%

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