Although the primary cause of this often devastating disease rema

Although the primary cause of this often devastating disease remains elusive, major therapeutic advances this website have occurred during the past two decades. Here, we present a review of current immunomodulatory treatments and outline upcoming therapy

approaches, including biologics and oral alternatives that might have equivalent or superior efficacy and/or enhanced tolerability compared with available treatments, and discuss the scientific rationale and expected benefits and risks for these compounds. We also speculate about alternatives beyond immune-directed approaches, review novel insights into the neurobiological consequences of sustained brain inflammation and evaluate future perspectives for neuroprotective and neuroregenerative treatment strategies for MS.”
“Altered levels of Substance P (SP), a neuropeptide E7080 in vitro endowed with neuroprotective and anti-apoptotic properties, were found in brain areas and spinal fluid of Alzheimer’s disease (AD) patients. One of the hallmarks of AD is the abnormal extracellular deposition of neurotoxic beta amyloid (A beta) peptides, derived from the proteolytic processing

of amyloid precursor protein (APP). In the present study, we confirmed, the neurotrophic action of SP in cultured rat cerebellar granule cells (CGCs) and investigated its effects on APP metabolism. Incubation with low (5 mM) potassium induced apoptotic cell death of CGCs and amyloidogenic processing of APP, whereas treatment with SP (200 nM) reverted these effects via NK1 receptors. The non-amyloidogenic effect of SP consisted of reduction of A beta(1-42), increase of sAPP alpha and enhanced alpha-secretase activity, without a significant change in steady-state levels of cellular APP. The intracellular ROS1 mechanisms whereby SP alters APP metabolism were further investigated by measuring mRNA and/or steady-state protein levels of key enzymes involved with alpha-, beta- and gamma-secretase activity. Among them, Adam9 both at the mRNA and protein level, was the

only enzyme to be significantly down-regulated following the induction of apoptosis (K5) and up-regulated after SP treatment. In addition to its neuroprotective properties, this study shows that SP is able to stimulate non-amyloidogenic APP processing, thereby reducing the possibility of generation of toxic A beta peptides in brain. (C) 2011 Elsevier Ltd. All rights reserved.”
“The increasing interest in the structural arrangements and functional interdependencies of individual modules within large multidomain proteins requires the development of new methods allowing efficient production and purification of large human proteins. Heterologous expression in bacteria is still the most convenient and widely-used approach.

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