Expert opinion on therapeutic targets
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Depression is one of the most prevalent and life-threatening forms of mental illness associated with significant disability and mortality. About 21% of the world's population is affected by depression. ⋯ Stress can be considered as a major contributor to the development of depressive disorder due to the dysregulation of HPA axis. Cytokine effects on behavior are believed to be related in part to their effects on neurotransmitter and neuropeptide function, synaptic plasticity and neuroendocrine function. Although there are multiple pathways that are involved in the pathogenesis of depression, the current antidepressants mainly target monoaminergic pathway. However, the therapeutic potential of other pathways is still under investigation. Drugs targeting NO, cytokines and the kynurenine acid pathway might be the drugs of choice in near future.
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Expert Opin. Ther. Targets · Dec 2010
EditorialAlzheimer's disease amyloid hypothesis at crossroads: where do we go from here?
Alzheimer's disease has been the focus of several drug discovery approaches by the pharmaceutical industry. Four drug candidates coming out of such efforts have recently failed in late-stage clinical trials for lack of efficacy or safety concerns. These drugs were designed based on the presently dominant scientific hypothesis for Alzheimer's disease called the 'amyloid hypothesis'. ⋯ Rather than accept the status quo, this editorial suggests a revised version of this hypothesis to reconcile data from recent drug failures. We propose a two-phase disease process; a first phase that is independent of amyloid and a second robust phase dependent on the amyloid cascade. Further validation of this revised hypothesis could aid future drug discovery for this devastating disease.
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Acute pancreatitis (AP) is a multifactorial disorder not fully understood yet. In particular, the pathogenetic pathways promoting a severe life-threatening course of AP are the subject of ongoing investigations. P-selectin has been shown to play a central role in the complex pathophysiology in AP as well as various other inflammatory conditions. ⋯ P-selectin is a glycoprotein that mediates the adhesion of activated platelets and leukocytes to the vessel wall in various inflammatory conditions. Both pathophysiological steps are closely linked and play a key role in the course of severe AP. A treatment approach by inhibition of P-selectin could be of distinct interest as a therapeutic option in severe AP.
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Expert Opin. Ther. Targets · Jan 2010
ReviewModulation of the renin-angiotensin-aldosterone system in sepsis: a new therapeutic approach?
Severe sepsis is characterized by relative hypotension associated with a high cardiac output, peripheral vasodilation, and organ dysfunction. The renin-angiotensin-aldosterone system (RAAS) is primarily activated to increase blood pressure, but recently potential pro-inflammatory effects of angiotensin II have attracted interest because of the reported association between angiotensin II levels and organ failure and mortality in sepsis. RAAS antagonists could represent a new therapeutic option in this setting. ⋯ Use of RAAS antagonists is an emerging therapeutic option in severe sepsis because these agents may reduce endothelial damage, organ failure, and mortality. However, timing of administration of RAAS antagonists is important because reduced RAAS function may contribute to refractive hypotension later on in septic shock and benefits of RAAS antagonists seem to be restricted to the early phases of sepsis.
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Expert Opin. Ther. Targets · Dec 2009
ReviewFactors that retard remyelination in multiple sclerosis with a focus on TIP30: a novel therapeutic target.
In the CNS oligodendrocytes produce myelin and ensheath individual axons after birth. Demyelination disables saltatory conduction and leads to loss of neural functions. Oligodendrocyte precursor cells (OPCs) are immature and abundant reservoir cells in the adult brain that are capable of differentiating into myelinating oligodendrocytes. ⋯ TIP30 inhibits proper nucleocytoplasmic transport and thus disables nuclear import of transcription factors that are required for differentiation. TIP30 may also increase susceptibility of OPCs to cell death. In this review, we examine the pathophysiological nature of remyelination failure in chronic MS and discuss the role of TIP30 as a novel therapeutic target.