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

Jul 22, 2014European journal of pharmacology

Curcumin may trigger cell recycling by lowering PI3K/Akt/mTOR pathway activity in Alzheimer's model mice

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Curcumin treatment improved cognitive function in APP/PS1 double transgenic Alzheimer's disease mice and inhibited Aβ generation.

Cognitive impairment was reduced, as measured by the Morris water maze test.
Curcumin treatment inhibited the generation of beta-amyloid, as shown by immunohistochemistry.
Curcumin induced autophagy in the mice, evidenced by analyses of a specific protein involved in the process.
Expression levels of key proteins associated with the PI3K/Akt/mTOR signaling pathway were significantly decreased.
Curcumin may act as a neuroprotective agent by promoting autophagy and inhibiting Aβ generation.

AI simplified

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.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

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

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief