BACKGROUND: Activation of @entity1110 oxidase (PHOX) plays a critical role in mediating dopaminergic neuroinflammation. In the present study, we investigated the role of PHOX in @entity888 (MA)-induced @entity2359 and inflammatory changes in @entity19 . METHODS: We examined changes in mitogen-activated protein kinases (MAPKs), mitochondrial function [i.e., mitochondrial membrane potential, intramitochondrial @entity141 accumulation, mitochondrial oxidative burdens, mitochondrial @entity224 dismutase expression, and mitochondrial translocation of the cleaved form of protein kinase C delta type (cleaved PKC  )], microglial activity, and pro-apoptotic changes [i.e., cytosolic cytochrome c release, cleaved caspase 3, and terminal deoxynucleotidyl transferase dUDP nick-end labeling (TUNEL) positive populations] after a @entity2359 dose of MA in the striatum of @entity19 to achieve a better understanding of the effects of @entity12824 , a non-specific PHOX inhibitor, or genetic inhibition of @entity19994 (by using @entity19994 knockout @entity19 or @entity19994 antisense oligonucleotide) against MA-induced dopaminergic @entity2359 . RESULTS: Phosphorylation of extracellular signal-regulated kinases ( @entity8837 ) was most pronounced out of MAPKs after MA. We observed MA-induced phosphorylation and membrane translocation of @entity19994 in the striatum of @entity19 . The activation of @entity19994 promoted mitochondrial stresses followed by microglial activation into the M1 phenotype, and pro-apoptotic changes, and led to @entity73 . @entity13436 activated these signaling pathways. @entity12824 or genetic inhibition of @entity19994 significantly protected these signaling processes induced by MA. @entity13436 inhibitor @entity5732 did not exhibit any additional positive effects against protective activity mediated by @entity12824 or @entity19994 genetic inhibition, suggesting that @entity13436 regulates @entity14099 phox activation, and @entity13436 constitutes the crucial target for @entity12824 -mediated inhibition of PHOX activation. CONCLUSIONS: Our results indicate that the neuroprotective mechanism of @entity12824 against MA insult is via preventing mitochondrial burdens, microglial activation, and pro-apoptotic signaling process by the @entity13436 -dependent activation of @entity19994 .

@entity12824 prevents mitochondrial burdens, microglial activation, and pro-apoptosis induced by a toxic dose of @entity888 in the striatum of @entity19 via inhibition of @entity14099 phox activation by XXXX .

@entity14099 :: ('386649(Tax:10090)', 'Gene') :: ['p47'] @entity5732 :: ('MESH:C113580', 'Chemical') :: ['U0126'] @entity12824 :: ('MESH:C056165', 'Chemical') :: ['Apocynin', 'apocynin'] @entity888 :: ('MESH:D008694', 'Chemical') :: ['methamphetamine'] @entity19994 :: ('17969(Tax:10090)', 'Gene') :: ['p47phox'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity8837 :: ('26417;26413', 'Gene') :: ['ERK1/2'] @entity73 :: ('MESH:D003072', 'Disease') :: ['dopaminergic impairments'] @entity1110 :: ('MESH:D009249', 'Chemical') :: ['NADPH'] @entity13436 :: ('26413(Tax:10090)', 'Gene') :: ['ERK'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity224 :: ('MESH:D013481', 'Chemical') :: ['superoxide'] @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxicity', 'neurotoxic']
@entity13436 :: (26413(Tax:10090),Gene) :: ['ERK']
