Monocarboxylate transporter 1 and the vulnerability of oligodendrocyte lineage cells to metabolic stresses.

Aims: Oligodendrocytes, especially oligodendrocyte precursor cells, are known to be sensitive to hypoxic and metabolic stresses. Vulnerability of oligodendrocytes is considered a contributing factor to white matter dysfunction. However, little is known about the energy processing characteristics of oligodendrocyte lineage cells under basal and metabolic stress conditions.

Inhibitors of enzymes catalyzing modifications to histone lysine residues: structure, function and activity.

Gene expression is partly controlled by epigenetic mechanisms including histone-modifying enzymes. Some diseases are caused by changes in gene expression that can be mitigated by inhibiting histone-modifying enzymes. This review covers the enzyme inhibitors targeting histone lysine modifications.

Nabilone as an adjunctive to gabapentin for multiple sclerosis-induced neuropathic pain: a randomized controlled trial.

Background: Neuropathic pain (NPP) is a chronic syndrome suffered by patients with multiple sclerosis (MS), for which there is no cure. Underlying cellular mechanisms involved in its pathogenesis are multifaceted, presenting significant challenges in its management.

Methods: A randomized, double-blind, placebo-controlled study involving 15 relapsing-remitting MS patients with MS-induced NPP was conducted to evaluate nabilone combined with gabapentin (GBP).

Elevated expression of fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) in the dorsal root ganglia and spinal cord in experimental autoimmune encephalomyelitis: implications in multiple sclerosis-induced neuropathic pain.

Multiple sclerosis (MS) is a central nervous system (CNS) disease resulting from a targeted autoimmune-mediated attack on myelin proteins in the CNS. The release of Th1 inflammatory mediators in the CNS activates macrophages, antibodies, and microglia resulting in myelin damage and the induction of neuropathic pain (NPP). Molecular signaling through fractalkine (CX3CL1), a nociceptive chemokine, via its receptor (CX3CR1) is thought to be associated with MS-induced NPP.

CXCL1 regulation of oligodendrocyte progenitor cell migration is independent of calcium signaling.

Cell migration is an indispensable aspect of tissue patterning during embryonic development. Oligodendrocytes, the myelinating cells of the central nervous system, migrate significantly during development of the brain. Several growth factors have been identified as being critical regulators of oligodendrocyte progenitor migration, including platelet derived growth factor-A (PDGFA), and fibroblast growth factor-2 (FGF2).

The role of dorsal root ganglia activation and brain-derived neurotrophic factor in multiple sclerosis.

Multiple sclerosis (MS) is characterized by focal destruction of the white matter of the brain and spinal cord. The exact mechanisms underlying the pathophysiology of the disease are unknown. Many studies have shown that MS is predominantly an autoimmune disease with an inflammatory phase followed by a demyelinating phase.

Examining the roles of cannabinoids in pain and other therapeutic indications: a review.

Importance Of The Field: In recent times, our knowledge of cannabinoids and the endocannabinoid system has greatly advanced. With expanding knowledge, synthetic cannabinoids - including nabilone, dronabinol and a combination of synthetic Delta9-THC and cannabidiol - have been developed and tested for benefit in a variety of therapeutic indications.

Areas Covered In This Review: The aim of this article is to provide a summative review of the vast amount of clinical trial data now available on these agents.

Examining the evidence: complementary adjunctive therapies for multiple sclerosis.

Objective: The purpose of this article is to provide a comprehensive overview of the most frequently encountered non-conventional approaches trialed for use in multiple sclerosis (MS). The efficacy and safety of non-conventional approaches ranging from bee venom therapy (BVT) to an array of vitamins and herbal products were discussed and evaluated.

Methods: Relevant English-language articles were identified through searches of MEDLINE (1990-2006), PubMed (1999-2006), Cochrane (1995-2006) and Toxnet (2000-2006).

The clinical importance of neutralizing antibodies in relapsing-remitting multiple sclerosis.

Background: Neutralizing antibodies (NAbs) develop in patients receiving interferon beta (IFN-beta) for multiple sclerosis (MS). Debate continues concerning the relevance of NAb development on treatment efficacy.

Objective: To determine the incidence and clinical importance of NAbs in patients with relapsing-remitting MS (RRMS).

Bone morphogenetic protein 4 mediates bile duct ligation induced liver fibrosis through activation of Smad1 and ERK1/2 in rat hepatic stellate cells.

Bone morphogenetic proteins (BMPs) are the important cytokine involving in cell differentiation especially in bone morphogenesis. Hepatic stellate cells (HSCs) undergo a trans-differentiation during their activation after liver injury. Although it has been demonstrated that BMP2 and BMP4 significantly increased the abundance of smooth muscle alpha actin (alpha-SMA) in cultured HSCs, the expression of BMPs has not been examined during the activation of HSCs.

A treatment algorithm for neuropathic pain.

Background: Neuropathic pain is a chronic pain syndrome caused by drug-, disease-, or injury-induced damage or destruction of sensory neurons within the dorsal root ganglia of the peripheral nervous system. Characteristic clinical symptoms include the feeling of pins and needles; burning, shooting, and/or stabbing pain with or without throbbing; and numbness. Neuronal hyperexcitability represents the hallmark cellular mechanism involved in the underlying pathophysiology of neuropathic pain.

CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion.

DNA microarray profiling of CD4(+) and CD8(+) cells from non-treated relapsing and remitting multiple sclerosis (MS) patients determined that the cytoplasmic binding partner of fragile X protein (CYFIP2, also called PIR121) was increased significantly compared to healthy controls. Western analysis confirmed that CYFIP2 protein was increased approximately fourfold in CD4(+) cells from MS compared to inflammatory bowel disorder (IBD) patients or healthy controls. Because CYFIP2 acts as part of a tetrameric complex that regulates WAVE1 activation we hypothesized that high levels of CYFIP2 facilitate T cell adhesion, which is elevated in MS patients.