Abstract:
:The deposition and accumulation of amyloid-beta-peptide (Abeta) in the brain are considered a sine qua non for Alzheimer's disease. The experimental delivery of fibrilized Abeta serves as a cellular model for several facets of the disease including the induction of synaptic dysfunction and apoptosis. c-Abl kinase is involved in the regulation of apoptosis and its pro-apoptotic function is in part mediated by its interaction with p73, a p53 homologue. We found that c-Abl activation is involved in cell signals that regulate neuronal death response to Abeta fibrils. Abeta peptide fibrils induced an increase of the c-Abl activity in rat hippocampal neurons as well as an increase in nuclear p73 protein levels and the p73-c-Abl complex. The neuronal cell death induced by Abeta fibrils was prevented by the inhibition of c-Abl with imatinib mesylate (Gleevec or STI571) and by the inhibition c-Abl expression by RNAi. These results directly point to a therapeutic strategy for the treatment of Alzheimer's disease.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Alvarez AR,Sandoval PC,Leal NR,Castro PU,Kosik KSdoi
10.1016/j.nbd.2004.06.007keywords:
subject
Has Abstractpub_date
2004-11-01 00:00:00pages
326-36issue
2eissn
0969-9961issn
1095-953Xpii
S0969-9961(04)00135-4journal_volume
17pub_type
杂志文章abstract::NMDA receptor dysfunction is central to the encephalopathies caused by missense mutations in the NMDA receptor subunit genes. Missense variants of GRIN1, GRIN2A, and GRIN2B cause similar syndromes with varying severity of intellectual impairment, autism, epilepsy, and motor dysfunction. To gain insight into possible b...
journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
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doi:10.1016/j.nbd.2012.03.023
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abstract::Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is widely expressed in brain tissue including neurons, glia, and endothelia in neurovascular units. It is a major source of oxidants in the post-ischemic brain and significantly contributes to ischemic brain damage. Inflammation occurs after brain ischemia and ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2011.01.027
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abstract::Focal mechanical cortical trauma triggers diffuse apoptotic neurodegeneration in the developing rat brain which is associated with invasion of brain tissue with inflammatory mediators. We hypothesized that caspase-1 and the two caspase-1-processed cytokines, interleukin (IL)-1beta and IL-18, are involved in trauma-ind...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.11.003
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2009.03.010
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.05.015
更新日期:2014-09-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2003.08.002
更新日期:2003-12-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2004.10.009
更新日期:2005-03-01 00:00:00
abstract::Familial amyotrophic lateral sclerosis (FALS) has been modeled in transgenic mice by introducing mutated versions of human genomic DNA encompassing the entire gene for Cu,Zn superoxide dismutase (SOD1). In this setting, the transgene is expressed throughout the body and results in mice that faithfully recapitulate man...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.06.005
更新日期:2005-12-01 00:00:00
abstract::Possible roles of the complement (C) system in the normal and injured brain were explored with inbred mice that carried a frameshift mutation in the C5 gene. A congenic pair was used: the C5-sufficient (C5+) B10.D2/nSnJ strain with the functional allele (Hc1) from the C57BL/10J donor strain was compared with the C5-de...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.1996.0020
更新日期:1996-01-01 00:00:00
abstract::Pituitary adenylate cyclase activating polypeptide (PACAP) and its complementary receptor, PAC1, are crucial in central respiratory control. PACAP Knockout (KO) mice exhibit a SIDS-like phenotype, with an inability to overcome noxious insults, compression of baseline ventilation, and death in the early post-neonatal p...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2017.04.002
更新日期:2017-07-01 00:00:00
abstract::Huntington's disease (HD) is a genetic neurodegenerative disease characterized by movement disorders, cognitive decline and neuropsychiatric symptoms. HD is caused by expanded CAG tract within the coding region of Huntingtin protein. Despite major insights into the molecular mechanisms leading to HD, no effective cure...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.04.007
更新日期:2012-08-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2008.03.011
更新日期:2008-07-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.12.012
更新日期:2013-06-01 00:00:00
abstract::We determined whether tetrahydrobiopterin(BH4), an endogenous cofactor for dopamine(DA) synthesis, causes preferential damage to DArgic neurons among primary cultured rat mesencephalic neurons and whether the death mechanism has relevance to Parkinson's disease (PD). DArgic neurons were more vulnerable to BH4 than non...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.08.024
更新日期:2007-01-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
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更新日期:2020-09-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.01.007
更新日期:2019-05-01 00:00:00
abstract::The focus on amyloid plaques and neurofibrillary tangles has yielded no Alzheimer's disease (AD) modifying treatments in the past several decades, despite successful studies in preclinical mouse models. This inconsistency has caused a renewed focus on improving the fidelity and reliability of AD mouse models, with dis...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
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journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
abstract::Spinal cord injury (SCI) is a major cause of disability, and at present, there is no universally accepted treatment. The functional decline following SCI is contributed to both direct mechanical injury and secondary pathophysiological mechanisms that are induced by the initial trauma. These mechanisms initially involv...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2003.11.015
更新日期:2004-04-01 00:00:00
abstract::Aberrant brain iron deposition is observed in both common and rare neurodegenerative disorders, including those categorized as Neurodegeneration with Brain Iron Accumulation (NBIA), which are characterized by focal iron accumulation in the basal ganglia. Two NBIA genes are directly involved in iron metabolism, but whe...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2015.12.004
更新日期:2016-03-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.03.013
更新日期:2016-07-01 00:00:00
abstract::Premature stop codons in CACNA1A, which encodes the alpha(1A) subunit of neuronal P/Q-type (Ca(V)2.1) Ca(2+) channels, cause episodic ataxia type 2 (EA2). CACNA1A undergoes extensive alternative splicing, which contributes to the pharmacological and kinetic heterogeneity of Ca(V)2.1-mediated Ca(2+) currents. We identi...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2008.06.002
更新日期:2008-10-01 00:00:00
abstract::The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are characterized by progressive neurodegeneration resulting in widespread brain atrophy. Each form is assumed to be the consequence of some universal intracellular event; however, time course studies on the cerebral cortex of a sheep model of the CLN6 form rev...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.11.008
更新日期:2011-03-01 00:00:00
abstract::Uridine, like adenosine, is released under sustained depolarization and it can inhibit hippocampal neuronal activity, suggesting that uridine may be released during seizures and can be involved in epileptic mechanisms. In an in vivo microdialysis study, we measured the extracellular changes of nucleoside and amino aci...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2004.02.011
更新日期:2004-08-01 00:00:00
abstract::Cholesterol precursors and cholesterol levels are reduced in brain regions of Huntington's disease (HD) mice. Here we quantified the rate of in vivo de novo cholesterol biosynthesis in the HD brain. Samples from different brain regions and blood of the heterozygous knock-in mouse model carrying 175 CAG repeats (Q175) ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.11.013
更新日期:2017-02-01 00:00:00
abstract::The present study aimed to evaluate the therapeutic potential of clioquinol (CQ), a metal chelator, on multiple sclerosis pathogenesis. Experimental autoimmune encephalomyelitis was induced by immunization with myelin oligodendrocyte glycoprotein (MOG(35-55)) in female mice. Three weeks after the initial immunization,...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.01.012
更新日期:2013-06-01 00:00:00