Immunoglobulins from patients with amyotrophic lateral sclerosis affect human erythrocyte acetylcholinesterase

Sindhuphak, Ratana; Karlsson, Evert; Conradi, S; Ronnevi, Lars‐Olof

doi:10.1016/0022-510x(88)90098-6

Cited by 12 publications

(6 citation statements)

References 20 publications

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“…The effect on survival was only observed with pre-symptomatic administration, a fact which potentially limits clinical therapeutic application of these results. Nevertheless, these data support the role of AChE in ALS pathogenesis, consistent with previous research linking AChE to neurodegeneration [3–7, 13–16]. …”

Section: Discussionsupporting

confidence: 91%

“…Furthermore, AChE has been shown to be present in tissues devoid of cholinergic synapses and to be involved in the process of apoptosis, a process also involved in ALS pathogenesis, by playing a pivotal role in apoptosome formation [5]. Clinical information is relatively sparse; elevated AChE levels were reported in the sera of ALS patients [6], as well as increased titers of IgG and IgA antibodies towards AChE [7]. Based on the circumstantial evidence linking AChE to ALS pathogenesis we sought to test the possibility that downregulation of AChE may be beneficial in an ALS mouse model.…”

Section: Introductionmentioning

confidence: 99%

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Presymptomatic Treatment with Acetylcholinesterase Antisense Oligonucleotides Prolongs Survival in ALS (G93A-SOD1) Mice

Guillaume

Rozenstein

Einstein

et al. 2013

BioMed Research International

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Objective. Previous research suggests that acetylcholinesterase (AChE) may be involved in ALS pathogenesis. AChE enzyme inhibitors can upregulate AChE transcription which in certain contexts can have deleterious (noncatalytic) effects, making them theoretically harmful in ALS, whilst AChE antisense-oligonucleotides (mEN101), which downregulate AChE may be beneficial. Our aim was to investigate whether downregulation of AChE using mEN101 is beneficial in an ALS mouse model. Methods. ALS (G93A-SOD1) mice received saline, mEN101, inverse-EN101, or neostigmine. Treatments were administered from 5 weeks. Disease-onset and survival were recorded. Additional mice were sacrificed for pathological analysis at 15 weeks of age. In a follow-up experiment treatment was started at the symptomatic stage at a higher dose. Results. mEN101 given at the presymptomatic (but not symptomatic) stage prolonged survival and attenuated motor-neuron loss in ALS mice. In contrast, neostigmine exacerbated the clinical parameters. Conclusions. These results suggest that AChE may be involved in ALS pathogenesis. The accelerated disease course with neostigmine suggests that any beneficial effects of mEN101 occur through a non-catalytic rather than cholinergic mechanism.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Presymptomatic Treatment with Acetylcholinesterase Antisense Oligonucleotides Prolongs Survival in ALS (G93A-SOD1) Mice

Guillaume

Rozenstein

Einstein

et al. 2013

BioMed Research International

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“…Neostigmine decreased the binding of immunoglobulins and thus, the effect provoked by them. In the second one the same method was used as in this work (SINDHUPHAK et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

IgG from Cows with Parturient Paresis Changes the Thermodynamic Behaviour of Bovine Erythrocyte Acetylcholinesterase

Axelsson

Yong

Karlsson

1990

Journal of Veterinary Medicine, Series B

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Summary Parturient paresis affects about 10% of all cows. The most common treatment is injection of various Ca‐salts and MgCl2 and about 80% recover after repeated injections. The effect of IgG on the Arrhenius plot of bovine erythrocyte AChE was studied. The plot was normal, i. e. biphasic (a broken line) in the presence of IgG from healthy cows. The highest concentration tested was 10 mg/ml. Before one injection of the Ca‐Mg solution 5 mg/ml IgG from sera of paretic cows (n=10) changed the Arrhenius plots to monophasic (linear). Thus, paretic cows have antibodies against AChE. After injection the change to linear plots was observed already with 1 mg/ml IgG. Apparently, the level of antibodies in serum affecting AChE increased about 5‐fold. This is considered to be due to dissociation of bound antibodies from various AChEs. All cows recovered after one injection and release of AChE antibodies might be important for the recovery. Incubation of blood from paretic cows (n = 3) with Ca‐salts and MgCl2 increased the amount of free AChE‐antibodies about twofold; the Arrhenius plots became linear at 2.5 mg/ml IgG compared with 5 mg/ml before the incubation. This should be due to release from AChEs on blood corpuscles as erythrocytes and lymphocytes. But the increase of antibodies after incubation of blood does not account for the whole increase following the treatment of paretic cows. AChE antibodies are probably also dissociated from other sites, such as neuromuscular junctions.

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“…These auto antibodies prevent the conformational changes of the AChE at break point in the Arrhenius plot (33 o C), which normally occurs in control AChE [71]. These auto antibodies prevent the conformational changes of the AChE at break point in the Arrhenius plot (33 o C), which normally occurs in control AChE [71].…”

Section: Clinical Aspect Of Achementioning

confidence: 99%

Specific Cholinesterase Inhibitors: A Potential Tool to Assist in Management of Alzheimer Disease

Grieg

Kamal

Jabir

et al. 2014

Drug Design and Discovery in Alzheimer's Disease

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Immunoglobulins from patients with amyotrophic lateral sclerosis affect human erythrocyte acetylcholinesterase

Cited by 12 publications

References 20 publications

Presymptomatic Treatment with Acetylcholinesterase Antisense Oligonucleotides Prolongs Survival in ALS (G93A-SOD1) Mice

Presymptomatic Treatment with Acetylcholinesterase Antisense Oligonucleotides Prolongs Survival in ALS (G93A-SOD1) Mice

IgG from Cows with Parturient Paresis Changes the Thermodynamic Behaviour of Bovine Erythrocyte Acetylcholinesterase

Specific Cholinesterase Inhibitors: A Potential Tool to Assist in Management of Alzheimer Disease

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