MAPT and hyperhomocysteinemia: Studies have shown that hyperhomocysteinemia may activate several protein kinases, such as glycogen synthase kinase 3β (GSK-3β), cyclin-dependent kinase-5 (Cdk-5), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase (MAPK), and inhibit protein phosphatase 2A (PP2A) (41), which are all pivotal enzymes in regulating the phosphorylation state of tau protein [65].