Heat Shock Protein Inspired Nanochaperones Restore Amyloid-β Homeostasis for Preventative Therapy of Alzheimer’s Disease
Open accessAbstract
Amyloid beta (Aβ) aggregation is generally believed as the crucial and primary cause of Alzheimer's disease (AD). However, current Aβ-targeted therapeutic strategies show limited disease-modifying efficacy due to the irreversible damages in the late stage of AD, thus the treatment should be given before the formation of deposition and target primary Aβ species rather than advanced plaques. Herein, inspired by heat shock protein, a self-assembly nanochaperone based on mixed-shell polymeric micelle (MSPM) is devised to act as a novel strategy for AD prevention. With unique surface hydrophobic domains, this nanochaperone can selectively capture Aβ peptides, effectively suppress Aβ aggregation, and remarkably reduce Aβ-mediated cytotoxicity. Moreover, the formed nanochaperone-Aβ complex after Aβ adsorption can be easily phagocytosed by microglia and thereby facilitates Aβ clearance. As a result, the nanochaperone reduces Aβ burden, attenuates Aβ-induced inflammation, and eventually rescues the cognitive deficits of APP/PS1 transgenic AD mice. These results indicate that this biomimetic nanochaperone can successfully prevent the onset of AD symptoms and serve as a promising candidate for prophylactic treatment of AD.
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Amyloidogenic proteins (Aβ) and tau are examples of heat-shock proteins (HSPs) that can both promote and inhibit the aggregation of misfolded proteins.
“Amyloidogenic proteins (Aβ) and tau are two examples of heat-shock proteins (HSPs) that can both promote and inhibit the aggregation of misfolded proteins [37,101].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [101]
Inadequate operation of HSP systems can lead to oxidative stress, mitochondrial dysfunction, and other pathological conditions that damage the body, cause neuronal death, and exacerbate dementia.
“Inadequate operation of these systems can lead to oxidative stress, mitochondrial dysfunction, and various other pathological conditions that damage the body, cause neuronal death, and exacerbate dementia.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [101]
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- Authors
- Yang, H., Li, X., Zhu, L., Wu, X., Zhang, S., Huang, F., Feng, X., & Shi, L.
- Affiliations
- Nankai University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Huang, Fan
- Feng, Xizeng
- Shi, Linqi
- Venue
- Advanced Science
- Publisher
- Wiley
- Published
- 2019-09-16
- Volume
- 6
- Issue
- 22
- Pages
- 1901844-1901844
- ISSN
- 2198-3844 (ISSN-L)
- PMC
- PMC6864524
- OpenAlex
- W2974574046
- Cited by
- 98
- References
- 51
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 20 · 2023: 13 · 2022: 17 · 2021: 16 · 2020: 13 · 2019: 1
- FWCI
- 8.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Advanced Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (91527306, 51390483, 51603231, 21620102005)
- Chinese Academy of Medical Sciences (2019‐RC‐HL‐014)
- Fundamental Research Funds for the Central Universities (3332018194, 3332018115)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta, amyloid-beta aggregation, amyloid-beta clearance, neuroinflammation, cognitive impairment, prophylaxis, biomimetic nanomaterials, APP/PS1 mice
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