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Discovering and targeting the basic mechanism of neurodegeneration: the role of peptides from the C-terminus of acetylcholinesterase: non-hydrolytic effects of ache: the actions of peptides derived from the C-terminal and their relevance to neurodegeneration
Greenfield S.. Chemico-biological interactions, 2013-04-03
Topic: Brain proteins, microglia and lab models
Acetylcholinesterase (AChE) is now well-established widely as a signalling molecule with non-hydrolytic functions including trophic activity in a diverse variety of situations in both neural and non-neural tissues. We have focussed on the observation that AChE, operating as a trophic agent independent of its enzymatic action, does indeed trigger calcium entry into neurons. It is possible that AChE has a dual non-classical action that ranges along a trophic-toxic axis, depending on amount, duration of availability and, most significantly, age. The neurodegenerative diseases could therefore be viewed as aberrant activation of developmental mechanisms with 'non-cholinergic' AChE as a, perhaps the, pivotal molecule. We have identified two peptides that could be cleaved from the C-terminus of T-AChE, one (T14), within the other (T30), and which have a strong sequence homology to the comparable region of beta-amyloid whilst the inert residue within the T30 sequence ('T15') acts as a control, and is without effect. We have subsequently been able to ascribe the trophic-toxic actions of the both T14 and T30 peptides to the modulation of calcium influx via an allosteric site on the alpha-7 nicotinic acetylcholine receptor (α7-nAChR). If the scenario described here is indeed the primary mechanism of neurodegeneration, then interception of the actions of the 'non-cholinergic' AChE-peptides T14 and T30 at the α7-nAChR, would be a promising novel therapy for arresting and stabilising cell loss in Alzheimer's disease, whereas detection of the peptides ideally in the blood, could provide a sensitive surrogate marker. If the marker was sensitive enough to be detected pre-symptomatically in a routine blood test, then the medication for arresting further cell loss could be initiated at that time, and the symptoms would never appear. This dual approach of identifying the marker and then intercepting its further action, could thus amount to an effective treatment for Alzheimer's and other neurodegenerative diseases.
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APA 7th
Greenfield, S. (2013). Discovering and targeting the basic mechanism of neurodegeneration: the role of peptides from the C-terminus of acetylcholinesterase: non-hydrolytic effects of ache: the actions of peptides derived from the C-terminal and their relevance to neurodegeneration. Chemico-biological interactions. https://doi.org/10.1016/j.cbi.2013.03.015
Vancouver
Greenfield S. Discovering and targeting the basic mechanism of neurodegeneration: the role of peptides from the C-terminus of acetylcholinesterase: non-hydrolytic effects of ache: the actions of peptides derived from the C-terminal and their relevance to neurodegeneration. Chemico-biological interactions. 2013. doi:10.1016/j.cbi.2013.03.015. PMID: 23562497.
BibTeX
@article{greenfield2013-23562497,
author = {Greenfield, S.},
title = {{Discovering and targeting the basic mechanism of neurodegeneration: the role of peptides from the C-terminus of acetylcholinesterase: non-hydrolytic effects of ache: the actions of peptides derived from the C-terminal and their relevance to neurodegeneration}},
journal = {Chemico-biological interactions},
year = {2013},
doi = {10.1016/j.cbi.2013.03.015},
pmid = {23562497},
url = {https://doi.org/10.1016/j.cbi.2013.03.015}
}
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Key findings
- It is possible that AChE has a dual non-classical action that ranges along a trophic-toxic axis, depending on amount, duration of availability and, most significantly, age.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Chemico-biological interactions) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2013 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23562497) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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