Home › Research › Treatments
Alzheimer's disease: targeting the glutamatergic system
Conway ME.. Biogerontology, 2020-02-11
Topic: Disease mechanisms in lab and animal studies
Alzheimer's disease (AD) is a debilitating neurodegenerative disease that causes a progressive decline in memory, language and problem solving. For decades mechanism-based therapies have primarily focused on amyloid β (Aβ) processing and pathways that govern neurofibrillary tangle generation. With the potential exception to Aducanumab, a monotherapy to target Aβ, clinical trials in these areas have been challenging and have failed to demonstrate efficacy. Currently, the prescribed therapies for AD are those that target the cholinesterase and glutamatergic systems that can moderately reduce cognitive decline, dependent on the individual. In the brain, over 40% of neuronal synapses are glutamatergic, where the glutamate level is tightly regulated through metabolite exchange in neuronal, astrocytic and endothelial cells. In AD brain, Aβ can interrupt effective glutamate uptake by astrocytes, which evokes a cascade of events that leads to neuronal swelling, destruction of membrane integrity and ultimately cell death. Much work has focussed on the post-synaptic response with little insight into how glutamate is regulated more broadly in the brain and the influence of anaplerotic pathways that finely tune these mechanisms. The role of blood branched chain amino acids (BCAA) in regulating neurotransmitter profiles under disease conditions also warrant discussion. Here, we review the importance of the branched chain aminotransferase proteins in regulating brain glutamate and the potential consequence of dysregulated metabolism in the context of BCAA or glutamate accumulation. We explore how the reported benefits of BCAA supplementation or restriction in improving cognitive function in other neurological diseases may have potential application in AD. Given that memantine, the glutamate receptor agonist, shows clinical relevance it is now timely to research related pathways, an understanding of which could identify novel approaches to treatment of AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Conway, M. E. (2020). Alzheimer's disease: targeting the glutamatergic system. Biogerontology. https://doi.org/10.1007/s10522-020-09860-4
Vancouver
Conway ME. Alzheimer's disease: targeting the glutamatergic system. Biogerontology. 2020. doi:10.1007/s10522-020-09860-4. PMID: 32048098.
BibTeX
@article{conway2020-32048098,
author = {Conway, M. E.},
title = {{Alzheimer's disease: targeting the glutamatergic system}},
journal = {Biogerontology},
year = {2020},
doi = {10.1007/s10522-020-09860-4},
pmid = {32048098},
url = {https://doi.org/10.1007/s10522-020-09860-4}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Much work has focussed on the post-synaptic response with little insight into how glutamate is regulated more broadly in the brain and the influence of anaplerotic pathways that finely tune these mechanisms.
- The role of blood branched chain amino acids (BCAA) in regulating neurotransmitter profiles under disease conditions also warrant discussion.
- Here, we review the importance of the branched chain aminotransferase proteins in regulating brain glutamate and the potential consequence of dysregulated metabolism in the context of BCAA or glutamate accumulation.
- We explore how the reported benefits of BCAA supplementation or restriction in improving cognitive function in other neurological diseases may have potential application in AD.
- Given that memantine, the glutamate receptor agonist, shows clinical relevance it is now timely to research related pathways, an understanding of which could identify novel approaches to treatment of AD.
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Evidence strengthLow
How this study scored 41/100
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 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biogerontology) |
| 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 | 2 / 5 | 2020 — within 10 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 32048098) |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related studies in Treatments
Also tagged “repurposing”
235 studies in the library carry the topic tag “repurposing”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 235 tagged studies.