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Parallel modulators such as brain-derived neurotrophic factor (BDNF) ( via tropomyosin receptor kinase B (TrkB)/AKT) and g protein-coupled receptor kinase 2 (GRK2) [which constrains p38-mitogen activated protein kinase (MAPK)] fine-tune the pathway in neural tissue, while AMPK provides an energy-status override that can suppress mTORC1 even when PI3K is active (Zhang HP