AMPK activation may disrupt neuronal proteostasis to promote neurodegeneration. a In neurodegenerative disorders, accumulation of protein aggregates and amyloids in neurons causes AMPK activation, which, in turn, may inactivate the HSF1-mediated PSR. This HSF1 inactivation leads to increased protein aggregates and amyloids, exacerbating neurotoxicity and neurodegeneration. b By contrast, AMPK inhibition may improve neuronal proteostasis by enhancing the HSF1-mediated PSR, thus representing a promising anti-neurodegeneration therapeutic strategy