title: Downregulation of PI3K/Akt/mTOR signaling pathway in curcumin-induced autophagy in APP/PS1 double transgenic mice.
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.
authors.affiliation: Department of Pathology, Yuanjiagang Yixueyuan Road NO. 1, Chongqing 400016, China; Institute of Neuroscience, Yuanjiagang Yixueyuan Road NO. 1, Chongqing 400016, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Yuanjiagang Yixueyuan Road NO. 1, Chongqing 400016, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Yuanjiagang Yixueyuan Road NO. 1, Chongqing 400016, China; Institute of Neuroscience, Yuanjiagang Yixueyuan Road NO. 1, Chongqing 400016, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Teng
authors.affiliation: Foreign languages Department, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Yuanjiagang Yixueyuan Road NO. 1, Chongqing 400016, China; Institute of Neuroscience, Yuanjiagang Yixueyuan Road NO. 1, Chongqing 400016, China. Electronic address: liyu100@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D003071:Cognition / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); C546843:mTOR protein, mouse; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D003474:Curcumin
keywords: AD; Autophagy; Aβ; Curcumin; PI3K/Akt/mTOR pathways