We propose that high-dose all-trans retinoic acid (ATRA) treatment, a derivative of retinoid, significantly induces glioblastoma cell apoptosis via caspase-dependent apoptosis, endoplasmic reticular (ER) stress, and intracellular reactive oxygen species (ROS) accumulation. The miR-302b overexpression enhanced by ATRA-mediated retinoic acid receptor (RAR)α pathway was also identified. The E2F3 repression, a novel target gene of miR-302b, was involved in ATRA-induced glioblastoma cell cytotoxicity.

Potential stress-sensitive sites were identified in differentiated human SH-SY5Y cells by the localization of HSPA6 (HSP70B') and HSPA1A (HSP70-1) to nuclear components following heat shock. HSPA6 and HSPA1A rapidly moved to nuclear speckles, enriched in RNA splicing factors, then to the granular layer of the nucleolus. Subsequently, HSPA6 exhibited a novel localization not observed for the more widely studied HSPA1A, namely association with the periphery of nuclear speckles that are sites of transcription. HS = heat shock; HSPA6 = HSP70B' protein; HSPA1A = HSP70-1 protein.

Noxious stimulation induces a slow-onset substance P (SP) release as a volume transmitter, activating extra-synaptic NK1 receptors, and evokes phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. The SP-NK1-ERK1/2 system in the striatum decreases tonic nociception.

We isolated a cDNA (Pr5-HT₈) from larval Pieris rapae, which shares relatively low similarity to the known GPCRs. After heterologous expression in HEK293 cells, Pr5-HT₈ mediated increased [Ca²⁺]_i in response to low concentrations (< 10 nM) of 5-HT and various 5-HT receptor agonists. We found orthologs of Pr5-HT₈ in some insect pests and vectors such as beetles and mosquitoes, but not in the genomes of honeybee, parasitoid wasps, or mammals.

We propose that the targeted suppression of glial heme oxygenase-1 (HO-1) hyperactivity may prove to be a rational and effective therapeutic intervention in Alzheimer's disease (AD) and related neurodegenerative disorders. We report attenuation by a selective HO-1 inhibitor of oxidative damage to whole-cell and mitochondrial compartments in astrocytes in vitro and amelioration of behavioral anomalies in a transgenic mouse model of AD.

Hyperammonemia, a proverbial main factor responsible for neurocognitive disorder and blood–brain barrier (BBB) dysfunction resulting from liver failure, could increase the expression and activity of P-glycoprotein and multidrug resistance-associated protein 2 (Mrp2) at the BBB both in vivo and in vitro. Furthermore, the NF-κB activation stimulated by hyperammonemia may be the potential mechanism underlying such abnormalities induced by hyperammonemia.

Activated microglial cells mediated neuroinflammatory events are observed in HIV-associated neurological disorders. The reduction in miR-17 levels was observed in microglial cells exposed to HIV-1 Tat C protein. miR-17 regulated the expression of NOX2 and NOX4, which in turn regulated the reactive oxygen species (ROS) production in microglial cells. Increased ROS production led to the activation of microglial cells and increased cytokine production. This study thus demonstrated a novel miR-17-mediated regulatory pathway of ROS production in microglial cells. HMC3 = human microglia clone 3 cell lines.

This study investigated the roles of transforming growth-interacting factor (TGIF) in a traumatic brain injury (TBI)-rat model. We demonstrated the increase of TGIF levels in the activated microglia of the pericontusional cortex of rats with TBI. Intracerebral knockdown of TGIF in the pericontusional cortex of the TBI rats significantly attenuated micoglial activation, reduced the volume of damaged brain tissue, and facilitated recovery of limb motor function. We suggest that inhibition of TGIF might provide a promising therapeutic strategy for TBI.

Blockade of brain melanocortine receptor 4 (MC4R) with intranasal infusion of the MC4R antagonist HS014 to rats prior to single prolonged stress (SPS) leads to faster termination of stress responses (30 min later) and prevents or attenuates SPS-triggered abnormal gene expression related to post-traumatic stress disorder (7 days later). Targeting of brain MC4R is a promising strategy to protect HPA axis, LC-NE (locus coeruleus-norepinephrine) systems and hippocampus from overstimulation.

We revealed signal transduction pathways that may promote sensitization of ethanol (EtOH)-induced place preference. EtOH facilitated the release of dopamine (DA) in the Nucleus accumbens (NAcc), enhancing calcineurin function via dopamine D1-like and D2-like receptor activation, which in turn resulted in increased NFATc4 expression. Increase in NFATc4 may further facilitate transcription factor binding to IP₃R-1 promoter domain to stimulate IP₃R-1 synthesis. Such increased IP₃R-1 elevates intracellular Ca²⁺ concentration via facilitated mobilization of Ca²⁺ from the intracellular Ca²⁺ stores to the cytosol.

The α-synuclein (SNCA) mutations, H50Q and G51D, cause Parkinson's disease. We found that H50Q increases and G51D decreases the rate of α-synuclein aggregation in vitro, and cells over-expressing the mutant proteins show decreased viability when stressed, compared to wild type. G51D is the first SNCA mutation to show decreased α-synuclein aggregation, suggesting a distinct disease mechanism to other SNCA mutations.

α-Synuclein is shown to cause mitochondrial impairment through interaction with permeability transition pore complex in isolated preparations. Intracellular accumulation of α-synuclein in SHSY5Y cells following proteasomal inhibition leads to mitochondrial impairment and cell death which could be prevented by knocking down α-synuclein gene. The results link mitochondrial dysfunction and α-synuclein accumulation, two key pathogenic mechanisms of Parkinson's disease, in a common damage pathway.