Abstract：
:For a long time, prolyl endopeptidase (PEP) was believed to inactivate neuropeptides in the extracellular space. However, reports on the intracellular activity of PEP suggest additional, as yet unidentified, physiological functions for this enzyme. Here, we demonstrate using biochemical methods of subcellular fractionation, immunocytochemical double-labelling procedures and localization of PEP-enhanced green fluorescent protein fusion proteins that PEP is mainly localized to the perinuclear space, and is associated with the microtubulin cytoskeleton in human neuroblastoma and glioma cell lines. Disassembly of the microtubules by nocodazole treatment disrupts both the fibrillar tubulin and PEP labelling. Furthermore, in a two-hybrid screen, PEP was identified as binding partner of tubulin. These findings indicate novel functions for PEP in axonal transport and/or protein secretion. Indeed, a metabolic labelling approach revealed that both PEP inhibition and PEP antisense mRNA expression result in enhanced peptide/protein secretion from human U-343 glioma cells. Because disturbances in intracellular transport and protein secretion mechanisms are associated with a number of ageing-associated neurodegenerative diseases, cell-permeable PEP inhibitors may be useful for the application in a variety of related clinical conditions.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Schulz I,Zeitschel U,Rudolph T,Ruiz-Carrillo D,Rahfeld JU,Gerhartz B,Bigl V,Demuth HU,Rossner Sdoi
10.1111/j.1471-4159.2005.03237.xkeywords:
subject
Has Abstractpub_date
2005-08-01 00:00:00pages
970-9issue
4eissn
0022-3042issn
1471-4159pii
JNC3237journal_volume
94pub_type
杂志文章abstract：:Progress has been made in Guillain-Barré syndrome, a post-infectious autoimmune neuropathy, especially on identifying Campylobacter jejuni genes responsible for the development and determinant of clinical features. C. jejuni strains carrying a sialyltransferase gene (cst-II), which is essential for the biosynthesis of...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
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abstract：:In the rat pilocarpine model, 1 h of status epilepticus caused significant inhibition of Mg(2+)/Ca(2+) ATPase-mediated Ca(2+) uptake in cortex endoplasmic reticulum (microsomes) isolated immediately after the status episode. The rat pilocarpine model is also an established model of acquired epilepsy. Several weeks aft...
journal_title：Journal of neurochemistry
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doi：10.1046/j.1471-4159.2001.00576.x
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journal_title：Journal of neurochemistry
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.65010192.x
更新日期：1995-07-01 00:00:00
abstract：:Larval zebrafish offers a good model to approach brain disease mechanisms, as structural abnormalities of their small brains can be correlated to quantifiable behavior. In this study, the structural alterations in one diencephalic dopaminergic nucleus induced by 1-methyl-4-phenylpyridinium (MPP+), a toxin inducing Par...
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更新日期：2009-02-01 00:00:00
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doi：10.1111/j.1471-4159.1990.tb08822.x
更新日期：1990-07-01 00:00:00
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doi：10.1111/j.1471-4159.1981.tb01732.x
更新日期：1981-03-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.01522.x
更新日期：2003-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02429.x
更新日期：2004-06-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12783
更新日期：2014-09-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb04739.x
更新日期：1982-07-01 00:00:00
abstract：:The study of aging is critical for a better understanding of many age-related diseases. The free radical theory of aging, one of the prominent aging hypotheses, holds that during aging, increasing reactive oxygen species in mitochondria causes mutations in the mitochondrial DNA and damages mitochondrial components, re...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02884.x
更新日期：2005-02-01 00:00:00
abstract：:Within the cell membrane there exist various microdomains (lipid rafts) in which specific lipids and proteins are assembled and these microdomains are recovered in the detergent-resistant low-density membrane fraction (DRM). Septin is a novel GTP-binding, cytoskeletal protein having various isoforms that assemble into...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2008.05450.x
更新日期：2008-08-01 00:00:00
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pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00064.x
更新日期：2001-02-01 00:00:00
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pub_type： 杂志文章
doi：10.1111/j.1471-4159.1993.tb09829.x
更新日期：1993-11-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
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更新日期：1994-08-01 00:00:00
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pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb05440.x
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb09283.x
更新日期：1992-01-01 00:00:00
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更新日期：2017-12-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb05388.x
更新日期：1984-11-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13921
更新日期：2017-02-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
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更新日期：2008-09-01 00:00:00
abstract：:For nearly 100 years following the first description of this neurological disorder by Dr Alois Alzheimer, amyloid plaques and neurofibrillary tangles have been hypothesized to cause neuronal loss. With evidence that the extent of insoluble, deposited amyloid poorly correlated with cognitive impairment, research effort...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
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更新日期：2012-01-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00356.x
更新日期：2001-06-01 00:00:00
abstract：:Tumor progression locus 2 (Tpl2)/cancer Osaka thyroid kinase is a newer member of MAP3K family that is now known for its essential role in tumor necrosis factor-aplha (TNFα) expression in macrophages, but its pro-inflammatory signaling, if any, in glia is unknown. When cultures of murine microglia and astrocytes were ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12522
更新日期：2014-03-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
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更新日期：1998-12-01 00:00:00
