Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatal murine cerebral malaria is an encephalitis and not simply a local manifestation in the brain of a systemic process. Histopathologically, murine cerebral malaria has been characterized by monocyte adherence to the endothelium of the microvasculature, activation of microglial cells, swelling of endothelial cell nuclei, microvasculature damage, and breakdown of the blood-brain barrier with cerebral oedema. Brain parenchymal cells have been proposed to be actively involved in the pathogenesis of murine cerebral malaria. We, therefore, compared the neurochemical characteristics of Plasmodium berghei ANKA-infected mice with controls to determine whether cerebral malarial infection significantly impairs specific neuronal populations. Between 6 and 7 days after infection, we found a significant loss of neurones containing substance P, with preservation of cells containing somatostatin, neuropeptide Y and calbindin in the striatum of infected mice compared with controls. In the cortex of infected mice, we found a significant reduction in the number of cells containing substance P, somatostatin and neuropeptide Y. The number of calbindin-containing neurones was unchanged. This study found significant changes in the neurochemical characteristics of the cortex and striatum of mice infected with P. berghei ANKA, which may contribute to their cerebral symptoms.
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PMID:Differences in the neurochemical characteristics of the cortex and striatum of mice with cerebral malaria. 1570 Jul 54

Multiple sclerosis is an autoimmune demyelinating disease of the central nervous system mainly mediated by Th1 and/or Th17 cells, which cross the blood-brain barrier. Recent evidence indicates that Th2 cells and mast cells, typically associated with allergic reactions, are also involved. Brain mast cells are critically located perivascularly and secrete numerous proinflammatory and vasoactive molecules that can disrupt the blood-brain barrier, a finding that precedes clinical or pathologic signs of multiple sclerosis. Brain mast cells in multiple sclerosis are activated by neural factors, including substance P, myelin basic protein, and corticotropin-releasing hormone, caused by acute stress, which induce release of several inflammatory mediators. Mast cells can stimulate activated T cells coming in contact with them at the blood-brain barrier, as well as after stimulation with myelin basic protein or substance P. Pretreatment with the flavone luteolin blocks mast cell stimulation and T cell activation, as well as experimental autoimmune encephalitis. Interactions between mast cells and T cells could constitute a new and unique therapeutic target for multiple sclerosis.
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PMID:Human mast cells stimulate activated T cells: implications for multiple sclerosis. 1907 66

The inflammatory responses of resident central nervous system (CNS) cells are now known to play a critical role in the initiation and progression of an array of infectious and sterile neuroinflammatory disorders such as meningitis, encephalitis, Parkinson's disease, Alzheimer's disease and multiple sclerosis (MS). Regulating glial inflammatory responses in a timely manner is therefore critical in preserving normal CNS functions. The neuropeptide substance P is produced at high levels within the CNS and its selective receptor, the neurokinin 1 receptor (NK-1R), is abundantly expressed by neurons and is present on glial cell types including microglia and astrocytes. In addition to its functions as a neurotransmitter in the perception of pain and its essential role in gut motility, this tachykinin is widely recognized to exacerbate inflammation at peripheral sites including the skin, gastrointestinal tract and the lungs. Recently, a number of studies have identified a role for substance P and NK-1R interactions in neuroinflammation and described the ability of this neuropeptide to alter the immune functions of activated microglia and astrocytes. In this review article, we describe the expression of substance P and its receptor by resident CNS cells, and we discuss the ability of this neuropeptide to exacerbate the inflammatory responses of glia and immune cells that are recruited to the brain during neurodegenerative diseases. In addition, we discuss the available data indicating that the NK-1R-mediated augmentation of such responses appears to be detrimental during microbial infection and some sterile neurodegenerative disorders, and propose the repurposed use of NK-1R antagonists, of a type that are currently approved as anti-emetic and anti-anxiolytic agents, as an adjunct therapy to ameliorate the inflammatory CNS damage in these conditions.
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PMID:The Therapeutic Potential of Targeting Substance P/NK-1R Interactions in Inflammatory CNS Disorders. 2810 Oct 5