Mammalian p38 mitogen-activated protein kinases (MAPKs) are activated by various cellular stresses, as well as in response to inflammatory cytokines. In the central nervous systems (CNS), activation of the p38 MAPK pathway constitutes a key step in the development of several diseases, and the molecular mechanisms mediated by p38 MAPK signaling have been defined. Activation of this cascade releases pro-inflammatory cytokines that are known to be involved in cerebral ischemia, Alzheimers disease (AD), Parkinsons disease (PD), multiple sclerosis (MS), neuropathic pain and depression. In AD, stimulated p38 MAPK may trigger the hyperphosphorylation of a neural microtubule-associated protein, tau. In addition, we have recently revealed that activation of p38 MAPK signaling decreases dendritic spine number, which may be associated with memory impairment after epileptic seizures. Thus, p38 MAPK can serve as a target for novel drug development for neural diseases. p38 MAPK inhibitors have been studied extensively in both preclinical experiments and clinical trials for inflammatory diseases. New p38 MAPK inhibitors are now being tested in phase II clinical trials for neuropathic pain and depression. Here, we review current and possible future applications of p38 MAPK inhibitors as therapeutic agents in neural diseases.

Syntenin is an adaptor-like molecule that has two adjacent tandem postsynaptic density protein 95/Discs large protein/Zonula occludens 1 (PDZ) domains. The PDZ domains of syntenin recognize multiple peptide motifs with low to moderate affinity. Many reports have indicated interactions between syntenin and a plethora of proteins. Through interactions with various proteins, syntenin regulates the architecture of the cell membrane. As a result, increases in syntenin levels induce the metastasis of tumor cells, protrusion along the neurite in neuronal cells, and exosome biogenesis in various cell types. Here, we review the updated data that support various roles for syntenin in the regulation of neuronal synapses, tumor cell invasion, and exosome control.

Several studies have reported an increased tendency towards anger in patients with panic disorder (PD). If this propensity for anger arises from the pathological process of PD, it may be associated with the duration of the illness. The present study therefore examined the relationship between duration of PD and the personality tendency to experience anger in PD patients. Participants were 413 patients (132 men and 281 women; age = 38.7 years) with PD. Diagnoses were confirmed using the Mini-International Neuropsychiatric Interview. Illness duration ranged from less than a year to 51 years. After participants completed the Revised NEO Personality Inventory, we examined the association between illness duration and the Angry Hostility and Impulsiveness subscale scores. In the analysis, participants were divided into two groups by duration of illness (long group, n = 186 and short group, n = 200) using the median value (9 years) as a cut-off because of the skewed distribution of the duration. Patients with an illness duration of 9 years (n = 27) were excluded from the comparison. The duration of illness was significantly correlated with the Angry Hostility score (p = 0.002) after controlling for age. Scores were significantly higher in the long group than in the short group (p = 0.04). No significant association was observed between Impulsiveness scores and duration of illness. The present study suggests that longer PD duration is related to a stronger tendency to experience anger.