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Multidimensional autophagy nano-regulator boosts Alzheimer's disease treatment by improving both extra/intraneuronal homeostasis
Yixian Li, Peng Yang, Ran Meng, Shuting Xu, Lingling Zhou, Kang Qian, Pengzhen Wang, Yunlong Cheng et al.. Acta pharmaceutica Sinica. B, 2023-10-21
Topic: Disease mechanisms in lab and animal studies
Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer's disease (AD) collectively culminate in neuronal deterioration. In the context of AD, autophagy dysfunction, a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological processes. Therefore, multidimensional autophagy regulation strategies co-manipulating "autophagy induction" and "lysosome degradation" in dual targets (neuron and microglia) are more reliable for AD treatment. Accordingly, we designed an RP-1 peptide-modified reactive oxygen species (ROS)-responsive micelles (RT-NM) loading rapamycin or gypenoside XVII. Guided by RP-1 peptide, the ligand of receptor for advanced glycation end products (RAGE), RT-NM efficiently targeted neurons and microglia in AD-affected region. This nano-combination therapy activated the whole autophagy-lysosome pathway by autophagy induction (rapamycin) and lysosome improvement (gypenoside XVII), thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes, and promoting Aβ phagocytosis. Resultantly, it decreased aberrant protein burden, alleviated neuroinflammation, and eventually ameliorated memory defects in 3 × Tg-AD transgenic mice. Our research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.
Key findings
- Accordingly, we designed an RP-1 peptide-modified reactive oxygen species (ROS)-responsive micelles (RT-NM) loading rapamycin or gypenoside XVII.
- Guided by RP-1 peptide, the ligand of receptor for advanced glycation end products (RAGE), RT-NM efficiently targeted neurons and microglia in AD-affected region.
- This nano-combination therapy activated the whole autophagy-lysosome pathway by autophagy induction (rapamycin) and lysosome improvement (gypenoside XVII), thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes, and promoting Aβ phagocytosis.
- Resultantly, it decreased aberrant protein burden, alleviated neuroinflammation, and eventually ameliorated memory defects in 3 × Tg-AD transgenic mice.
- Our research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.
Study details
- Evidence strengthLow
How this study scored 43/100
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, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta pharmaceutica Sinica. B) |
| 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 | 4 / 5 | 2024 — within 3 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 38486986) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Li, Y., Yang, P., Meng, R., Xu, S., Zhou, L., Qian, K., et al. (2024). Multidimensional autophagy nano-regulator boosts Alzheimer's disease treatment by improving both extra/intraneuronal homeostasis. Acta pharmaceutica Sinica. B. https://doi.org/10.1016/j.apsb.2023.10.009
Vancouver
Li Y, Yang P, Meng R, Xu S, Zhou L, Qian K, et al. Multidimensional autophagy nano-regulator boosts Alzheimer's disease treatment by improving both extra/intraneuronal homeostasis. Acta pharmaceutica Sinica. B. 2024. doi:10.1016/j.apsb.2023.10.009. PMID: 38486986.
BibTeX
@article{li2024-38486986,
author = {Li, Yixian and Yang, Peng and Meng, Ran and Xu, Shuting and Zhou, Lingling and Qian, Kang and Wang, Pengzhen and Cheng, Yunlong and others},
title = {{Multidimensional autophagy nano-regulator boosts Alzheimer's disease treatment by improving both extra/intraneuronal homeostasis}},
journal = {Acta pharmaceutica Sinica. B},
year = {2024},
doi = {10.1016/j.apsb.2023.10.009},
pmid = {38486986},
url = {https://doi.org/10.1016/j.apsb.2023.10.009}
}
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