AMPK signaling is preserved in tissues from CR animals, maintaining the integrity of the energy metabolism and the efficiency of fat metabolism. AMPK Signaling, a fuel sensor and regulator, promotes ATP-producing and inhibits ATP-consuming pathways in various tissues.
AMP-activated protein kinase (AMPK) is a central regulator of cellular energy homeostasis, playing critical roles in regulating growth and reprogramming metabolism as well as in cellular processes including autophagy and cell polarity.
The kinase is activated in response to stresses that deplete cellular ATP supplies such as low glucose, hypoxia, ischemia, and heat shock. As a cellular energy sensor responding to low ATP levels, AMPK activation positively regulates signaling pathways that replenish cellular ATP supplies. For example, activation of AMPK enhances both the transcription and translocation of GLUT4, resulting in an increase in insulin-stimulated glucose uptake.
AMPK is a heterotrimeric protein complex that is formed by α, β, and γ subunits. Each of these three subunits take on a specific role in both the stability and activity of AMPK.
As the figure shows, AMPK activation works via direct phosphorylation of multiple enzymes directly involved in these processes as well as through transcriptional control of metabolism by phosphorylating transcription factors, co-activators, and co-repressors. Because of its role in regulating energy homeostasis, AMPK is considered a potential target in the development of new treatments for obesity, type 2 diabetes, the metabolic syndrome, and cancer.
For cancer, on one hand, AMPK can protect against cell damage due to oxidative stress, which in turn protects against cancer and tumor initiation. On the other, AMPK promotes energy/glucose uptake by the cells, which can be used by a tumor once it has formed.
In a word, AMPK activation is deemed beneficial for the prevention of cancer, but not for its treatment. On the contrary, AMPK inhibition may be helpful for treating established cancers as it can help inhibit the survival and adaptation of tumor stress.
However, when it comes to neurodegenerative diseases, AMPK has both contributing and protective properties. However, studies often have opposing conclusions as regard this enzyme and its actual role.
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