Regulated neuronal cell death plays an essential role in biological processes in normal physiology, including the development of the nervous system. However, the deregulation of neuronal apoptosis by various factors leads to neurodegenerative diseases such as ischemic stroke and Alzheimer’s disease (AD). Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin (Ca²⁺/CaM)-dependent serine/threonine (Ser/Thr) protein kinase that activates death signaling and regulates apoptotic neuronal cell death. Although DAPK1 is tightly regulated under physiological conditions, DAPK1 deregulation in the brain contributes to the development of neurological disorders. In this review, we describe the molecular mechanisms of DAPK1 regulation in neurons under various stresses. We also discuss the role of DAPK1 signaling in the phosphorylation-dependent and phosphorylation-independent regulation of its downstream targets in neuronal cell death. Moreover, we focus on the major impact of DAPK1 deregulation on the progression of neurodegenerative diseases and the development of drugs targeting DAPK1 for the treatment of diseases. Therefore, this review summarizes the DAPK1 phosphorylation signaling pathways in various neurodegenerative diseases.

EPA, an omega-3 polyunsaturated fatty acid, exerts beneficial effects on human health. However, the molecular mechanisms underlying EPA function are poorly understood. The object was to illuminate molecular mechanism underlying EPA’s role. Here, ¹H-NMR-based metabolic analysis showed enhanced branched-chain amino acids (BCAAs) and lactate following EPA treatment in skeletal muscle cells. EPA regulated mitochondrial oxygen consumption rate. Furthermore, EPA induced calcium/calmodulin-dependent protein kinase kinase (CaMKK) through the generation of intracellular calcium. This induced the phosphorylation of AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK) that led to glucose uptake, and the translocation of glucose transporter type 4 (GLUT4) in muscles. In conclusion, EPA exerts benign effects on glucose through the activation of AMPK-p38 MAPK signaling pathways in skeletal muscles.