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Modulation of insulin signaling rescues BDNF transport defects independent of tau in amyloid-β oligomer-treated hippocampal neurons
Takach O, Gill TB, Silverman MA.. Neurobiology of aging, 2014-12-03
Topic: Brain proteins, microglia and lab models
Defective brain insulin signaling contributes to the cognitive deficits in Alzheimer's disease (AD). Amyloid-beta oligomers (AβOs), the primary neurotoxin implicated in AD, downregulate insulin signaling by impairing protein kinase B/AKT, thereby overactivating glycogen synthase kinase-3β. By this mechanism, AβOs may also impair axonal transport before tau-induced cytoskeletal collapse and cell death. Here, we demonstrate that a constitutively active form of protein kinase B/AKT prevents brain-derived neurotrophic factor (BDNF) transport defects in AβO-treated primary neurons from wild type (tau(+/+)) and tau knockout (tau(-/-)) mice. Remarkably, inhibition of glycogen synthase kinase-3β rescues BDNF transport defects independent of tau. Furthermore, exendin-4, an anti-diabetes agent, restores normal BDNF axonal transport by stimulating the glucagon-like peptide-1 receptor to activate the insulin pathway. Collectively, our findings indicate that normalized insulin signaling can both prevent and reverse BDNF transport defects in AβO-treated neurons. Ultimately, this work may reveal novel therapeutic targets that regulate BDNF trafficking, promote its secretion and uptake, and prolong neuronal survival during AD progression.
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APA 7th
Takach, O., Gill, T. B., & Silverman, M. A. (2015). Modulation of insulin signaling rescues BDNF transport defects independent of tau in amyloid-β oligomer-treated hippocampal neurons. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2014.11.018
Vancouver
Takach O, Gill TB, Silverman MA. Modulation of insulin signaling rescues BDNF transport defects independent of tau in amyloid-β oligomer-treated hippocampal neurons. Neurobiology of aging. 2015. doi:10.1016/j.neurobiolaging.2014.11.018. PMID: 25543463.
BibTeX
@article{takach2015-25543463,
author = {Takach, O. and Gill, T. B. and Silverman, M. A.},
title = {{Modulation of insulin signaling rescues BDNF transport defects independent of tau in amyloid-β oligomer-treated hippocampal neurons}},
journal = {Neurobiology of aging},
year = {2015},
doi = {10.1016/j.neurobiolaging.2014.11.018},
pmid = {25543463},
url = {https://doi.org/10.1016/j.neurobiolaging.2014.11.018}
}
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Key findings
- Collectively, our findings indicate that normalized insulin signaling can both prevent and reverse BDNF transport defects in AβO-treated neurons.
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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 randomized / 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 multicenter 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 (Neurobiology of aging) |
| 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 | 2015 — 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) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25543463) |
| 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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