Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response.

Anemoside A3 (AA3) is a natural triterpenoid glycoside isolated from the root of Pulsatilla chinensis (Bunge) Regel. We previously showed that AA3 exhibits cognitive-enhancing and neuroprotective properties. In the present study, we demonstrated that AA3 modulates inflammatory responses by regulating prostaglandin E receptor 4 signaling.

Diarylheptanoids from Rhizomes of Alpinia officinarum Inhibit Aggregation of α-Synuclein.

Two new diarylheptanoids, alpinin A (1) and alpinin B (2), together with 18 known diarylheptanoids (3-20), were isolated from the rhizomes of Alpinia officinarum. Their structures were elucidated by comprehensive spectroscopic analysis, including high-resolution mass spectrometry, infrared spectroscopy, and one- and two-dimensional nuclear magnetic resonance spectroscopy. Structurally, alpinin A is a new member of the small family of oxa-bridged diarylheptanoids and contains the characteristic 2,6-cis-configured tetrahydropyran motif (C-C oxa bridge).

Plant alkaloids as drug leads for Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative illness associated with dementia and is most prevalent among the elderly population. Current medications can only treat symptoms. Alkaloids are structurally diverse and have been an important source of therapeutics for various brain disorders.

Cycloastragenol is a potent telomerase activator in neuronal cells: implications for depression management.

Cycloastragenol (CAG) is an aglycone of astragaloside IV. It was first identified when screening Astragalus membranaceus extracts for active ingredients with antiaging properties. The present study demonstrates that CAG stimulates telomerase activity and cell proliferation in human neonatal keratinocytes.

Cdk5-dependent Mst3 phosphorylation and activity regulate neuronal migration through RhoA inhibition.

The radial migration of newborn neurons is critical for the lamination of the cerebral cortex. Proper neuronal migration requires precise and rapid reorganization of the actin and microtubule cytoskeleton. However, the underlying signaling mechanisms controlling cytoskeletal reorganization are not well understood.

Coronin 6 regulates acetylcholine receptor clustering through modulating receptor anchorage to actin cytoskeleton.

The maintenance of a high density of neurotransmitter receptors at the postsynaptic apparatus is critical for efficient neurotransmission. Acetylcholine receptors (AChRs) are neurotransmitter receptors densely packed on the postsynaptic muscle membrane at the neuromuscular junction (NMJ) via anchoring onto the actin cytoskeletal network. However, how the receptor-associated actin is coordinately regulated is not fully understood.

Olean-12-eno[2,3-c] [1,2,5]oxadiazol-28-oic acid (OEOA) induces G1 cell cycle arrest and differentiation in human leukemia cell lines.

Oleanolic acid (3β-hydroxy-olea-12-en-28-oic acid) is a natural pentacyclic triterpenoic acid found in many fruits, herbs and medicinal plants. In the past decade, increasing evidence has suggested that oleanolic acid exhibits inhibitory activities against different types of cancer including skin cancer and colon cancer, but not leukemia. We report here that a derivative of oleanolic acid, olean-12-eno[2,3-c] [1], [2], [5]oxadiazol-28-oic acid (designated OEOA) effectively blocks the proliferation of human leukemia cells.

Cdk5-mediated phosphorylation of Axin directs axon formation during cerebral cortex development.

Axon formation is critical for the establishment of connections between neurons, which is a prerequisite for the development of neural circuitry. Kinases such as cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase-3β (GSK-3β), have been implicated to regulate axon outgrowth. Nonetheless, the in vivo roles of these kinases in axon development and the underlying signaling mechanisms remain essentially unknown.

Differential and synergistic effect of nerve growth factor and cAMP on the regulation of early response genes during neuronal differentiation.

Neurotrophin (NT)-driven differentiation is a process involving activation of multiple signalling events. Treatment of PC12 cells with the prototypic NT nerve growth factor (NGF) induces PC12 cell differentiation characterized by neurite outgrowth and expression of differentiation genes. Cyclic AMP (cAMP), one of the second messengers of NGF stimulation, has also been observed to induce neuronal differentiation in PC12 cells.

Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons.

Neurotrophins are key regulators of neuronal survival and differentiation during development. Activation of their cognate receptors, Trk receptors, a family of receptor tyrosine kinases (RTKs), is pivotal for mediating the downstream functions of neurotrophins. Recent studies reveal that cyclin-dependent kinase 5 (Cdk5), a serine/threonine kinase, may modulate RTK signaling through phosphorylation of the receptor.

STAT3 as a downstream mediator of Trk signaling and functions.

Signal transducer and activator of transcription 3 (STAT3) has long been shown to regulate gene transcription in response to cytokines and growth factors. Recent evidence suggests that STAT3 activation may also occur downstream of receptor-tyrosine kinase activation. In the current study we have identified STAT3 as a novel signal transducer for TrkA, the receptor-tyrosine kinase that mediates the functions of nerve growth factor (NGF).

SLAM-associated protein as a potential negative regulator in Trk signaling.

Neurotrophin signaling plays important roles in regulating the survival, differentiation, and maintenance of neurons in the nervous system. Binding of neurotrophins to their cognate receptors Trks induces transactivation and phosphorylation of the receptor at several tyrosine residues. These phosphorylated tyrosine residues then serve as crucial docking sites for adaptor proteins containing a Src homology 2 or phosphotyrosine binding domain, which upon association with the receptor initiates multiple signaling events to mediate the action of neurotrophins.

Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of transcription 3 and regulates its transcriptional activity.

The activity of cyclin-dependent kinase 5 (Cdk5) depends on the association with one of its activators, p35 and p39, which are prominently expressed in the nervous system. Studies on the repertoire of protein substrates for Cdk5 have implicated the involvement of Cdk5 in neuronal migration and synaptic plasticity. Our recent analysis of the sequence of signal transducer and activator of transcription (STAT)3, a key transcription factor, reveals the presence of potential Cdk5 phosphorylation site.

Leukemia inhibitory factor receptor signaling negatively modulates nerve growth factor-induced neurite outgrowth in PC12 cells and sympathetic neurons.

Nerve growth factor (NGF) is required for the development of sympathetic neurons and subsets of sensory neurons. Our current knowledge on the molecular mechanisms underlying the biological functions of NGF is in part based on the studies with PC12 rat pheochromocytoma cells, which differentiate into sympathetic neuron-like cells upon NGF treatment. Here we report that the expression of leukemia inhibitory factor receptor (LIFR), one of the signaling molecules shared by several neuropoietic cytokines of the interleukin-6 family, is specifically up-regulated in PC12 cells following treatment with NGF.