1,721,093 research outputs found
. Impact of apoE genotype on circulating IL-18 and Amyloid beta levels in Alzheimer’s disease
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A pathophysiological role for selective alteration of the cytokine-chemokine network - inflammatory theory in Alzheimer's disease
No full textThere is growing evidence that an altered metabolism of the amyloid β (Aβ) precursor protein (APP) with progressive deposition of its Aβ fragment is a crucial event in the pathogenesis of AD. Increasing evidence suggests that inflammation and alteration of the cytokine-chemokine network contributes to the pathophysiology of AD. Activated microglia produce multiple pro-inflammatory cytokines, chemokines and reactive oxygen species (ROS); additionally, Aβ itself can stimulate microglia, astrocytes and oligodendrocytes to secrete pro-inflammatory cytokines, chemokines and ROS, which can lead to neuronal damage. The concomitant release of pro-inflammatory cytokines, which influence neurodegenerative pathways, and anti-inflammatory cytokines may contribute to the chronicity of the disease. It is the balance of pro-inflammatory products and anti-inflammatory products that may be essential in the degenerative process. Influencing this balance may help in slowing the disease. Promising results for neurological disease treatment may be achieved by targeting cytokines and chemokines in the development of antagonists and synthesis inhibitor
New Pharmacological Approaches to the Cholinergic System: An Overview on Muscarinic Receptor Ligands and Cholinesterase Inhibitors.
No full textThe cholinergic system is expressed in neuronal and in non-neuronal tissues. Acetylcholine (ACh), synthesized in and out of the nervous system can locally contribute to modulation of various cell functions (e.g. survival, proliferation). Considering that the cholinergic system and its functions are impaired in a number of disorders, the identification of new pharmacological approaches to regulate cholinergic system components appears of great relevance. The present review focuses on recent pharmacological drugs able to modulate the activity of cholinergic receptors and thereby, cholinergic function, with an emphasis on the muscarinic receptor subtype, and additionally covers the cholinesterases, the main enzymes involved in ACh hydrolysis.
The presence and function of muscarinic receptor subtypes both in neuronal and non-neuronal cells has been demonstrated using extensive pharmacological data emerging from studies on transgenic mice. The possible involvement of ACh in different pathologies has been proposed in recent years and is becoming an important area of study. Although the lack of selective muscarinic receptor ligands has for a long time limited the definition of therapeutic treatment based on muscarinic receptors as targets, some muscarinic ligands such as cevimeline (patents US4855290; US5571918) or xanomeline (patent, US5980933) have been developed and used in pre-clinical or in clinical studies for the treatment of nervous system diseases (Alzheimer’ and Sjogren’s diseases). The present review focuses on the potential implications of muscarinic receptors in different pathologies, including tumors. Moreover, the future use of muscarinic ligands in therapeutic protocols in cancer therapy will be discussed, considering that some muscarinic antagonists currently used in the treatment of genitourinary disease (e.g. darifenacin, patent, US5096890; US6106864) have also been demonstrated to arrest tumor progression in nude mice.
The involvement of muscarinic receptors in nociception also is over-viewed. In fact, muscarinic agonists such as vedaclidine, CMI-936 and CMI-1145 have been demonstrated to have analgesic effects in animal models comparable or more pronounced to those produced by morphine or opiates.
Likewise, the crucial role of cholinesterases (acetylcholinesterase and butirylcholinesterase) in neural transmission is discussed, as large number of drugs inhibiting cholinesterase activity have become of increasing relevance particularly for the treatment of neurodegenerative disorders. Herein we summarize the current knowledge of the cholinesterase inhibitors with particular attention to recent patents for Alzheimer’s disease drugs
Probiotics and anti-inflammatory processes in HIV infection: from Benchside Research to Bedside
No full textThe Food and Agriculture Organization and the World Health Organization have defined probiotics as: “live microorganisms which when administered in adequate amounts confer a health benefit on the host”. Infection with HIV results in a defective immunological function of T cells and macrophages as well as in cytokine dysregulation with increased production of pro-inflammatory cytokines. Based on the capacity to stimulate immune and non-immune cells, probiotics may have anti-inflammatory effects. Both in vitro and in vivo studies have shown that probiotics may lower systemic inflammation, acting on Th1, Th2, Th17, Treg cell production, NK cell activity and cytokines production
Editorial: Neurodegenerative Disorders: Synthesis, Drug Delivery Strategies and Biological Evaluation of New Therapeutic Agents
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