Current Pharmaceutical Design - Volume 13, Issue 24, 2007

Intracellular Ca2+ release channels, such as inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), facilitate the release of Ca2+ from intracellular storage organelles in response to extracellular and intracellular stimuli. Consequently, these large, tetrameric proteins play a central role in Ca2+ signalling and Ca2+ homeostasis in virtually all cells. Recent data suggests that intracellular Ca2+ release channel Read More

Pulmonary arterial hypertension (PAH) is a disease characterized by a progressive increase in pulmonary arterial pressure leading to right ventricular hypertrophy, right heart failure and ultimately to death. PAH is a disease of small pulmonary arteries inducing vascular narrowing leading to a progressive increase in pulmonary vascular resistance. The therapeutic means that improve PAH are still very limited and a Read More

Ion channels are ubiquitous transmembrane proteins that are involved in a wide variety of cellular functions by selectively controlling the passage of ions across the plasma membrane. Among these functions many immune processes, including those in autoimmune reactions, also rely on the operation of ion channels, but the roles of ion channels can be very diverse. Here the participation of ion channels in three different role Read More

While thought to be irremediable for a long time, nervous system lesions are may be close to be treatable. This hope comes from the fantastic progress in identifying the molecular nature of neurite growth inhibitory factors accumulated in the lesion sites and contributing to the lack of nerve regeneration. A wide range of secreted or membrane bound factors have been shown to trigger growth inhibitory pathways. In parallel t Read More

Functional recovery following acute CNS injury in humans, such as spinal cord injury and stroke, is exceptionally limited, leaving the affected individual with life-long neurological deficits such as loss of limb movement and sensation leading to a compromised quality of life. As yet, there is no effective treatment on the market for such injuries. This lack of functional recovery can at least in part be attributed to the restriction Read More

The presence of numerous axon-inhibitory molecules limits the capacity of injured neurons in the adult mammalian central nervous system (CNS) to regenerate damaged axons. Among others, chondroitin sulphate proteoglycans (CSPGs) enriched in glycosaminoglycan (GAG) chains, acting intracellularly via Rho GTPase activation and cytoskeletal modification, prevent axon re-growth after injury. However, axon regeneration Read More

Several myelin-associated proteins in the central nervous system (CNS) have been identified as inhibitors of axonal regeneration following the injury of the adult vertebrate CNS. Among these inhibitors, myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte- myelin glycoprotein (OMgp) are well characterized. Recently, the repulsive guidance molecule (RGM) was included as a potent myelin-derived neurite outgrowth inhi Read More

Vaccines have been considered in treating many CNS degenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), epilepsy, multiple sclerosis (MS), spinal cord injury (SCI), and stroke. DNA vaccines have emerged as novel therapeutic agents because of the simplicity of their generation and application. Myelin components such as NOGO, MAG and OMGP are known to tri Read More

Recent work indicates that the expression of Eph and ephrin proteins is upregulated after injury in the central nervous system (CNS). Although to date, much of the interest in these protein families in the nervous system has been on their roles during development, their presence in the adult CNS at multiple time points after injury suggest that they play significant roles in key aspects of the nervous system's response to dama Read More

The nanodelivery of therapeutics into the brain will require a step-change in thinking; overcoming the blood brain barrier is one of the major challenges to any neural therapy. The promise of nanotechnology is that the selective delivery of therapeutics can be delivered through to the brain without causing secondary damage. There are several formidable barriers that must be overcome in order to achieve axonal regenerati Read More

It has long been recognized that the central nervous system (CNS) exhibits only limited capacity for axonal regeneration following injury. It has been proposed that myelin-associated inhibitory molecules are responsible for the nonpermissive nature of the CNS environment to axonal regeneration. Experimental strategies to enhance regeneration by neutralizing these inhibitory molecules are rapidly advancing toward clinical applica Read More