Abstract：
:Discovery of new central nervous system (CNS) acting therapeutics has been slowed down by the lack of useful applicable biomarkers of disease or drug action often due to inaccessibility of relevant human CNS tissue and cell types. In recent years, non-neuronal cells, such as astrocytes, have been reported to play a highly significant role in neurodegenerative diseases, CNS trauma, as well as psychiatric disease and have become a target for small molecule and biologic therapies. We report the development of a method for measuring pharmacodynamic changes induced by potential CNS therapeutics using nasal olfactory neural tissue biopsy. We validated this approach using a potential astrocyte-targeted therapeutic, thiamphenicol, in a pre-clinical rodent study as well as a phase 1 human trial. In both settings, analysis of the olfactory epithelial tissue revealed biological activity of thiamphenicol at the drug target, the excitatory amino acid transporter 2 (EAAT2). Therefore, this biomarker approach may provide a reliable evaluation of CNS glial-directed therapies and hopefully improve throughput for nervous system drug discovery.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Sattler R,Ayukawa Y,Coddington L,Sawa A,Block D,Chipkin R,Rothstein JDdoi
10.1016/j.expneurol.2011.09.002subject
Has Abstractpub_date
2011-12-01 00:00:00pages
203-11issue
2eissn
0014-4886issn
1090-2430pii
S0014-4886(11)00309-8journal_volume
232pub_type
临床试验,杂志文章abstract：:Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for nigrostriatal dopaminergic, central cholinergic, and motoneurons. GDNF also prevents the neuronal loss in experimental animal models for Parkinson's disease (PD). We have now investigated the GDNF gene for possible mutations in a group ...
journal_title：Experimental neurology
pub_type： 杂志文章
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journal_title：Experimental neurology
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abstract：BACKGROUND:Cognitive impairment in humans with Alzheimer's disease (AD) and in animal models of Aβ-pathology can be ameliorated by treatments with the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ) agonists, such as rosiglitazone (RSG). Previously, we demonstrated that in the Tg2576 animal mo...
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journal_title：Experimental neurology
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journal_title：Experimental neurology
pub_type： 杂志文章,评审
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.2002.7884
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journal_title：Experimental neurology
pub_type： 杂志文章,评审
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abstract：:Patients with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) often experience increased sensory responsiveness in the urinary bladder reflecting neurogenic bladder overactivity. Here we demonstrate that colitis-induced up-regulation of the phospholipase C gamma (PLCγ) pathway downstream of brain-de...
journal_title：Experimental neurology
pub_type： 杂志文章
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更新日期：2016-11-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.2001.7854
更新日期：2002-03-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1993.1005
更新日期：1993-01-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2007.03.015
更新日期：2007-06-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2006.08.004
更新日期：2007-01-01 00:00:00
abstract：:Recent evidence suggests interactions between primary afferent nociceptors and postganglionic sympathetic efferents in the pathogenesis of inflammation. The effect of unilateral removal of the superior cervical ganglion on the innervation pattern of nerve fibers immunoreactive (IR) to calcitonin gene-related peptide (...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.2001.7642
更新日期：2001-05-01 00:00:00
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(91)90128-y
更新日期：1991-06-01 00:00:00
abstract：:Convection-enhanced delivery has recently entered the clinic and represents a promising new therapeutic option in the field of neurodegenerative diseases and treatment of brain tumors. Understanding of the principles governing delivery and flow of macromolecules within the CNS is still poorly understood and requires m...
journal_title：Experimental neurology
pub_type： 杂志文章
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更新日期：2005-11-01 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Experimental neurology
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journal_title：Experimental neurology
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journal_title：Experimental neurology
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journal_title：Experimental neurology
pub_type： 杂志文章
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abstract：:The progressive loss of the nigrostriatal pathway is a distinguishing feature of Parkinson's disease. Because terminal field loss appears to precede cell body loss, we tested whether the mouse mutant Wld(S), which delays axonal degeneration in a variety of disorders, would ameliorate nigrostriatal degeneration followi...
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