Cited by 125Alzheimer's disease research and treatmentsAutophagy in Disease and TherapyGraphene and Nanomaterials Applications

Single-Walled Carbon Nanotubes Alleviate Autophagic/Lysosomal Defects in Primary Glia from a Mouse Model of Alzheimer’s Disease

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Xue, Xue, Wang, Li-Rong, Sato, Yutaka, Jiang, Ying, Berg, Martin, Yang, Dun-Sheng, Nixon, Ralph A., Liang, Xing-Jie·2014·Nano Letters

Abstract

Defective autophagy in Alzheimer’s disease (AD) promotes disease progression in diverse ways. Here, we demonstrate impaired autophagy flux in primary glial cells derived from CRND8 mice that overexpress mutant amyloid precursor protein (APP). Functionalized single-walled carbon nanotubes (SWNT) restored normal autophagy by reversing abnormal activation of mTOR signaling and deficits in lysosomal proteolysis, thereby facilitating elimination of autophagic substrates. These findings suggest SWNT as a novel neuroprotective approach to AD therapy.

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  • Lysosomal pH and CTSD activity are impaired in primary glia cultured from brains of a mutant APP model of AD (CRND8).

    “Lysosomal pH and CTSD activity are similarly, impaired in primary glia cultured from brains of a mutant APP model of AD (CRND8) (Xue et al., 2014).”

    From Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99) (2019) · cites this paper as Xue et al., 2014

    In “CRND8 Glia Exhibit Lysosomal Dysfunction, Which Is Reversed by SWNT” (page unavailable), the paper reports markedly decreased active cathepsin D in primary CRND8 glia. It also reports impaired CatD maturation and discusses lysosomal acidification, but the available passages do not establish impaired lysosomal pH as a separate finding. (LLM, conf=0.83)

    Experimental — accuracy not yet measured
  • The findings support an emerging concept that acidification impairment may be a proximal biochemical event in AD, common to multiple genetic risk factors that cause or promote AD.

    “The findings support an emerging concept that acidification impairment may be a proximal biochemical event in AD, common to multiple genetic risk factors that cause or promote AD (Lee et al., 2010;Xue et al., 2014;Vidoni et al., 2016).”

    From Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99) (2019) · cites this paper as Xue et al., 2014

    The Abstract and the section “CRND8 Glia Exhibit Lysosomal Dysfunction, Which Is Reversed by SWNT” link mutant APP in an AD mouse model to lysosomal dysfunction, and the Figure 1 description suggests that restoring lysosomal acidification may improve proteolysis (page numbers unavailable). The paper does not establish acidification impairment as a proximal event in AD or show that it is common to multiple genetic risk factors; it studies glia from one mutant-APP mouse model. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Xue, X., Wang, L.-R., Sato, Y., Jiang, Y., Berg, M., Yang, D.-S., Nixon, R. A., & Liang, X.-J.
Affiliations
  • Nathan Kline Institute for Psychiatric Research (US)
  • National Center for Nanoscience and Technology of China , , ,
  • Nathan Kline Institute , , , ,
  • National Center for Nanoscience and Technology (CN)
Corresponding author
  • Nixon, Ralph A.
  • Liang, Xing-Jie
Venue
Nano Letters
Published
2014-08-12
Volume
14
Issue
9
Pages
5110-5117
ISSN
  • 1530-6984 (ISSN-L)
  • 1530-6992
OpenAlex
W2321720205
Cited by
125
References
64
Citations by year
2026: 2 · 2025: 7 · 2024: 12 · 2023: 12 · 2022: 12 · 2021: 13 · 2020: 11 · 2019: 14 · 2018: 11 · 2017: 16 · 2016: 13 · 2015: 2
FWCI
6.89
Type
journal article
Language
en
Open access
Locations
  • Nano Letters (publishedVersion, other-oa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (P01AG017617)
  • National Natural Science Foundation of China (31225009, 81171455)
  • Chinese Academy of Sciences (07165111ZX, 2012AA020804, SS2014AA020708, XDA09030301)
  • Ministry of Science and Technology of the People's Republic of China (2009CB930200)
  • Takeda Pharmaceutical Company Limited (NA)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Physical Sciences › Engineering › Biomedical Engineering › Graphene and Nanomaterials Applications
Keywords
single-walled carbon nanotubes, Alzheimer's disease, autophagy, lysosomal proteolysis, glial cells, amyloid precursor protein, mTOR signaling, neuroprotection, functionalized nanotubes
MeSH terms
Alzheimer Disease, Animals, Autophagy, Biocompatible Materials, Disease Models, Animal, Lysosomes, Mice, Transgenic, Neuroglia, Signal Transduction, Disease Progression, Nanotechnology, Nanotubes, Carbon, Mice, TOR Serine-Threonine Kinases

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