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These data were in line with the hypothesis that neuromuscular junctions, which are the synapses between MNs and muscle fiber, could represent the starting site of MN dysfunction in ALS [269]

The mitochondrial creatine kinase isoform (mtCK), in particular, forms a multienzyme complex with the adenine nucleotide translocator (ANT) and the voltage-dependent anion channel (VDAC), effectively coupling mitochondrial ATP synthesis to cytosolic ATP utilization [11]

ENO1 suppression could also be associated with apoptosis induction by curcumin probably mediated through p38 mitogen-activated protein kinase (MAPK) activation and 5 adenosine monophosphate-activated protein kinase (AMPK) dephosphorylation [117]

Table 2 Therapeutic strategies targeting hypoxic microenvironment in rheumatoid arthritis