Publication date: Mar 10, 2020
AMPK positively regulates catabolic pathways such as fatty acid oxidation and autophagy when the concentration of intracellular ATP is low, while it negatively affects anabolic pathways such as glycogen synthesis, de novo synthesis of triglycerides, fatty acids, and cholesterol.
A number of such naturally occurring compounds are attracting the attention of researchers in preventing diseases through activation of AMPK.
For instance, a study carried out on rodent models for Alzheimer’s disease and Huntington’s disease, demonstrated that administration of resveratrol, a sirtuin 1 activator, reduced neurodegeneration that can be partially attributed to AMPK activation.
The therapeutic effects of resveratrol were attributed to activation of AMPK through autophagy, antioxidant gene expression, and mitochondrial biogenesis.
AMPK activation in cancer therapy: To enhance the efficacy of combination drugs used in cancer treatment, and to prevent multidrug resistance, a number of studies have been looking at using AMPK regulators for targeted therapy.
Although the molecular mechanism is yet to be understood with certainty, metformin positively influences activation of AMPK and can be investigated further in cancer prevention and treatment.
Although AMPK activation is being researched extensively for cancer therapy, activation of AMPK can sometimes promote the proliferation of cancer cells.
In prostate cancer cases, AMPK activation will cause elevation of Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ) expression thereby causing further proliferation of prostate cancer cells.
This shows the complexity involved in cancer therapy using AMPK activation where tumor suppression would depend on the type of pathway and cancer cells involved.
A number of substrates of AMPK are now known to be involved in maintaining activities such as growth, metabolism, autophagy, and cell polarity.
What remains a challenge, and needs to be investigated further, are targets that bring about therapeutic effects upon activation of AMPK in neurodegenerative disorders, metabolic disorders, and cancer.
|drug||DRUGBANK||Dextrose unspecified form|
|disease||MESH||type 2 diabetes|
|pathway||KEGG||AMPK signaling pathway|
|disease||MESH||small cell lung carcinoma|