Abstract：
:The presence of the alpha2macroglobulin receptor/low density lipoprotein receptor-related protein (alpha2Mr/LRP) and its ligands alpha2macroglobulin (alpha2M), apoliprotein E, and plasminogen activators was detected in senile plaques of Alzheimer's disease (AD). To explore a possible role of alpha2M in neurodegenerative processes occurring in AD, we analyzed the effect of alpha2M on Abeta 25-35-induced neurotoxicity. Treatment of LAN5 human neuroblastoma cells with 10 microM beta-amyloid peptide fragment 25-35 (Abeta 25-35) for 72 h resulted in a 50% decrease in cell viability as determined by MTT incorporation and cell counts. The addition of alpha2M to the culture medium of these cells did not determine any effect, but when the activated form alpha2M* was used a dose-dependent decrease in cell viability was observed, the maximum effect being reached at 140 and 280 nM. Moreover, treatment of LAN5 cells with alpha2M* in combination with Abeta 25-35 increased the neurotoxicity of the amyloid peptide by 25%. This neurotoxic effect of alpha2M* seems to be related to its capability to bind and inactivate TGFbeta in the culture medium, since it was mimicked by a TGFbeta neutralizing antibody. A possible involvement of receptor-mediated endocytosis was ruled out, since alpha2M receptor is not present on LAN5, as revealed by RT-PCR and Western blotting experiments. The presence of alpha2M* in amyloid deposits of Alzheimer's disease has been recently reported and a possible impairment of LRP internalization processes has been hypothesized. Our data suggest that the local accumulation of alpha2M* in AD plaques may increase Abeta 25-35-induced neurotoxicity by neutralizing TGFbeta-mediated neuroprotective mechanisms.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Fabrizi C,Businaro R,Lauro GM,Starace G,Fumagalli Ldoi
10.1006/exnr.1998.6978keywords:
subject
Has Abstractpub_date
1999-02-01 00:00:00pages
252-9issue
2eissn
0014-4886issn
1090-2430pii
S0014-4886(98)96978-3journal_volume
155pub_type
杂志文章abstract：:A neurochemical target at which cannabinoids interact to have global effects on behavior is brain noradrenergic circuitry. Acute and repeated administration of a cannabinoid receptor synthetic agonist is capable of increasing multiple indices of noradrenergic activity. This includes cannabinoid-induced 1) increases in...
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abstract：:Blood flow in the feline thoracic spinal cord was measured, using a laser-Doppler flowmetry. Rhythmic changes in the spinal cord blood flow were repeatedly observed with a frequency of about three to eight cycles per minute, unrelated to the respiratory or cardiac cycles. These changes were unaffected by hypertension ...
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
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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
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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
doi：10.1016/0014-4886(87)90233-0
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2007.01.030
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(91)90066-l
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abstract：:We have investigated the formation of DNA adducts and oxidative base damage produced by copper sulfate activation of dopamine and 6-hydroxydopamine. In the presence of 10 microM copper sulfate both 100 microM dopamine and 100 microM 6-hydroxydopamine formed three similar DNA adducts with relative adduct levels of 8.36...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1997.6560
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abstract：:Recent in vitro studies have shown that the periventricular subependymal zone (SEZ) of the rodent brain is capable of de novo generation of neurons and glia. There is less information available on neurogenesis in the adult human brain, and no study has shown the clonal generation of neurons and glia from in vitro-gene...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1999.7028
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abstract：:The behavioral effects of augmenting dopamine D1 receptor expression in the brain were investigated in mice incorporating additional copies of the mouse D1 receptor gene. Two transgenic lines showed increases in brain D1 receptor binding sites, which were greatest in extrastriatal regions. The full D1 agonist SKF 8129...
journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1006/exnr.1999.7037
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journal_title：Experimental neurology
pub_type： 杂志文章
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abstract：:Adeno-associated virus (AAV) vectors are derived from a nonpathogenic and defective human parvovirus. Although currently unable to display the integration specificity featured by its wild-type parent, the recombinant AAV (rAAV) system has continued to attract enormous interest primarily due to its unique features such...
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
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doi：10.1006/exnr.2000.7425
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journal_title：Experimental neurology
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doi：10.1006/exnr.1994.1092
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/0014-4886(92)90004-a
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journal_title：Experimental neurology
pub_type： 杂志文章
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journal_title：Experimental neurology
pub_type： 杂志文章
doi：10.1016/j.expneurol.2005.01.014
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journal_title：Experimental neurology
pub_type： 杂志文章
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abstract：:The GluN2 subunits that compose N-methyl-d-aspartate receptors (NMDARs) are attractive drug targets for therapeutic intervention in several diseases, in particular Parkinson's disease (PD). The precise roles and possible dysfunctions of NMDARs attributed to specific GluN2 subunits are however unresolved. Through the u...
journal_title：Experimental neurology
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doi：10.1016/j.expneurol.2014.03.001
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