The Bewildering Effect of AMPK Activators in Alzheimer’s Disease: Review of the Current Evidence

Table 2

Summary of the positive and negative effects of AMPK activators.

Positive effects	Negative effects
Inhibit BACE enzyme expression at translation level [53, 55]	Enhance BACE mRNA transcription [77]
Enhance autophagic clearance of Aβ and aggregated tau [71, 73]	Excessive autophagy-mediated secretion of Aβ [76]
Increased IDE expression and Aβ degradation [75]	AMPK directly phosphorylates tau proteins at sites which affect microtubule association [157]
Decrease the activity of GSK3β and thereby decrease tau phosphorylation [104, 225]
Increase the activity of PP2A and facilitate the dephosphorylation of tau proteins [104]
Activate SIRT1 and facilitate tau clearance through ubiquitin-proteasomal system [114, 148]
Halt oxidative stress by reducing ROS production, activating antioxidant enzymes, enhancing the expression of antioxidants, and stimulating autophagic clearance [190, 205, 214, 219]