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This is not surprising because the cellular and molecular adaptations underlying tolerance almost certainly do not have a unitary mechanism, and different cell lines, different neurons and neuronal compartments (i.e., terminal versus somatic compartments) may express different levels of regulatory proteins

Osredkar J

While preclinical studies suggest neuroprotective benefits, long-term clinical data in humans are limited, and further research is needed to determine whether these effects occur via the gut-brain axis or direct antioxidant activity

Xing Y, Musi N, Fujii N, Zou L, Luptak I, Hirshman MF, Goodyear LJ, Tian R (2003) Glucose metabolism and energy homeostasis in mouse hearts overexpressing dominant negative alpha2 subunit of AMP-activated protein kinase