Molecular interactions of acetylcholinesterase with senile plaques

Inestrosa, Nibaldo C.; Alarcón, Rodrigo

doi:10.1016/s0928-4257(99)80002-3

Cited by 58 publications

(43 citation statements)

References 15 publications

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“…Later utilization of simple separation methods revealed a broad family of cholinesterases and the existence of several catalytically active AChE isoforms that could be distinguished by velocity sedimentation, gel electrophoresis, and their different solubility in diverse buffers, allowing the individual biochemical characterization of each of the forms. Molecular cloning of the ACHE genes from Torpedo californica (Schumacher et al 1986(Schumacher et al , 1988 and humans (Soreq et al 1990;Ben Aziz-Aloya et al 1993) preceded the determination of the three-dimensional structure of the enzyme (Sussman et al 1991) and the later identification of the anchoring molecules linking the diverse AChE multi-extend previous reports (Layer 1996;Inestrosa and Alarcon 1998;Day and Greenfield 2002;Soreq and Seidman 2001) asserting that AChE functions go far beyond the termination of synaptic transmission.…”

Section: Introductionmentioning

confidence: 66%

Termination and beyond: acetylcholinesterase as a modulator of synaptic transmission

2006

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Termination of synaptic transmission by neurotransmitter hydrolysis is a substantial characteristic of cholinergic synapses. This unique termination mechanism makes acetylcholinesterase (AChE), the enzyme in charge of executing acetylcholine breakdown, a key component of cholinergic signaling. AChE is now known to exist not as a single entity, but rather as a combinatorial complex of protein products. The diverse AChE molecular forms are generated by a single gene that produces over ten different transcripts by alternative splicing and alternative promoter choices. These transcripts are translated into six different protein subunits. Mature AChE proteins are found as soluble monomers, amphipatic dimers, or tetramers of these subunits and become associated to the cellular membrane by specialized anchoring molecules or members of other heteromeric structural components. A substantial increasing body of research indicates that AChE functions in the central nervous system go far beyond the termination of synaptic transmission. The non-enzymatic neuromodulatory functions of AChE affect neurite outgrowth and synaptogenesis and play a major role in memory formation and stress responses. The structural homology between AChE and cell adhesion proteins, together with the recently discovered protein partners of AChE, predict the future unraveling of the molecular pathways underlying these multileveled functions.

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Section: Introductionmentioning

confidence: 66%

Termination and beyond: acetylcholinesterase as a modulator of synaptic transmission

2006

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“…95,96 Supporting this is the observation that AChE colocalizes with Aβ deposits in the AD brain. 97 AChE may bind to a protease-sensitive nonamyloidogenic conformer of Aβ and induce a conformational transition into a partly protease-resistant amyloidogenic conformer of Aβ, and thus to amyloid fibrils. 98 Therefore, AChE directly promotes the formation of amyloid fibrils and stable Aβ-AChE complexes.…”

Section: Potential Effects On Disease Progressionmentioning

confidence: 99%

Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

Grossberg

2003

Current Therapeutic Research

286

156

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Background: Cholinesterase (ChE) inhibitors currently used in the treatment of Alzheimer's disease (AD) are the acetylcholinesterase (AChE)-selective inhibitors, donepezil and galantamine, and the dual AChE and butyrylcholinesterase (BuChE) inhibitor, rivastigmine. In addition to differences in selectivity for AChE and BuChE, ChE inhibitors also differ in pharmacokinetic and pharmacodynamic properties, and these differences could significantly impact on safety, tolerability, and efficacy.Objective: The aim of this article was to provide an overview of the ChE inhibitors widely used in AD, focusing on key pharmacologic differences among agents and how these may translate into important differences in safety, tolerability, and efficacy in clinical practice.Methods: Using published literature collected over time by the author, a review was conducted, focusing on the pharmacology and clinical data of donepezil, galantamine, and rivastigmine.

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“…In addition to the key role of AChE in cholinergic function, the correct orientation of AChE catalytic subunits at the cell surfaces of certain neurons, targeted by PRiMA, is proposed to be required for neurite outgrowth (7). Additionally, G 4 AChE in the brain is related to amyloid plaques and neurofibrillary tangles in Alzheimer disease and may contribute to its development (8). Thus, G 4 AChE may have distinct functions in different tissues.…”

mentioning

confidence: 99%

Regulation of a Transcript Encoding the Proline-rich Membrane Anchor of Globular Muscle Acetylcholinesterase

Xie

Choi

Leung

et al. 2007

Journal of Biological Chemistry

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AChE in cultured myotubes were markedly reduced. In addition, calcitonin gene-related peptide, a known motor neuron-derived factor, and muscular activity were able to suppress PRiMA expression in muscle; the suppression was mediated by the phosphorylation of a cAMP-responsive element-binding protein. In accordance with the in vitro results, sciatic nerve denervation transiently increased the expression of PRiMA mRNA and decreased the phosphorylation of cAMP-responsive element-binding protein as well as its activator calcium/calmodulin-dependent protein kinase II in muscles. Our results suggest that the expression of PRiMA, as well as PRiMA-associated G 4 AChE, in muscle is suppressed by muscle regulatory factors, muscular activity, and nerve-derived trophic factor(s).

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Molecular interactions of acetylcholinesterase with senile plaques

Cited by 58 publications

References 15 publications

Termination and beyond: acetylcholinesterase as a modulator of synaptic transmission

Termination and beyond: acetylcholinesterase as a modulator of synaptic transmission

Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

Regulation of a Transcript Encoding the Proline-rich Membrane Anchor of Globular Muscle Acetylcholinesterase

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