Cited by 234Alzheimer's disease research and treatmentsCurcumin's Biomedical ApplicationsAutophagy in Disease and Therapy

Downregulation of PI3K/Akt/mTOR signaling pathway in curcumin-induced autophagy in APP/PS1 double transgenic mice

Wang, Chen, Zhang, Xiong, Teng, Zhipeng, Zhang, Tong, Li, Yu·2014·European Journal of Pharmacology

Abstract

Autophagy is a lysosomal degradation pathway, which is essential for cell survival, proliferation, differentiation and homeostasis. It is well known that beta-amyloid (Aβ) aggregation is one of key characteristics for Alzheimer's disease (AD), which triggers a complex pathological cascade, leading to neurodegeneration. Recent studies have shown that Aβ peptide is generated from amyloid β precursor protein (APP) during autophagic turnover of APP-rich organelles by autophagy. Aβ generation during normal autophagy is subsequently degraded by lysosomes. Curcumin, a nature plant extraction, has been reported to inhibit the generation and deposition of Aβ; however, the underlying mechanisms are not fully understood yet. In the present study, we reported that curcumin treatment not only attenuated cognitive impairment detected by Morris water maze test, but also inhibited the generation of Aβ investigated by immunohistochemistry in APP/PS1 double transgenic AD mice. Moreover, curcumin induced autophagy in the mice, evidenced by LC3 immunofluorescence analysis and western blot assays on LC3. Furthermore, we found that curcumin significantly decreased the expression of Phosphatidylinositol 3-Kinase (PI3K), phosphorylated Akt and rapamycin (mTOR) at protein levels, respectively. Taken together, our data suggests that curcumin inhibits Aβ generation and induces of autophagy by downregulating PI3K/Akt/mTOR signaling pathway, and further shows a neuroprotective effect. Meanwhile curcumin might be a candidate neuroprotective agent for AD patients treatment by inducing autophagy.

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Crossref · 10.1016/j.ejphar.2014.06.051

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Authors
Wang, C., Zhang, X., Teng, Z., Zhang, T., & Li, Y.
Affiliations
Chongqing Medical University (CN)
Corresponding author
Li, Yu
Venue
European Journal of Pharmacology
Publisher
Elsevier BV
Published
2014-10
Volume
740
Pages
312-320
ISSN
0014-2999 (ISSN-L)
OpenAlex
W2008391194
Cited by
233
References
32
Citations by year
2026: 12 · 2025: 24 · 2024: 16 · 2023: 12 · 2022: 29 · 2021: 24 · 2020: 29 · 2019: 22 · 2018: 18 · 2017: 20 · 2016: 15 · 2015: 11 · 2014: 1
FWCI
10.45
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81100948, 81271426)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Curcumin's Biomedical Applications
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
curcumin, autophagy, PI3K/AKT/mTOR pathway, Alzheimer's disease, APP/PS1 double transgenic mice, cognitive impairment, neuroprotection, LC3, rapamycin, amyloid precursor protein
MeSH terms
Beclin-1, Alzheimer Disease, Animals, Autophagy, Cognition, Curcumin, Disease Models, Animal, Female, Hippocampus, Male, Memory, Mice, Transgenic, Peptide Fragments, Signal Transduction, Down-Regulation, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Neuroprotective Agents, Maze Learning, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-akt, Presenilin-1, Phosphatidylinositol 3-Kinase, TOR Serine-Threonine Kinases

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