Abstract:
:Mutations in the DNA-binding domain of EGR2 are associated with severe autosomal dominant forms of peripheral neuropathy. In this study, we show that one such Egr2 mutant (S382R, D383Y), when expressed in Schwann cells in vitro, is not transcriptionally inactive but retains residual wild-type Egr2 functions, including inhibition of transforming growth factor-beta-induced Schwann cell death and an ability to induce the cytoskeletal protein periaxin. More importantly, this mutant Egr2 has aberrant effects in Schwann cells, enhancing DNA synthesis both in the presence and absence of the putative axonal mitogen, beta-neuregulin 1. This is in stark contrast to wild-type Egr2, which causes withdrawal from the cell cycle. Furthermore, mutant Egr2 upregulates cyclin D1 and reduces levels of the cell cycle inhibitor, p27. These observations add significant new evidence to explain how this mutation leads to congenital hypomyelinating neuropathy in humans.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Arthur-Farraj P,Mirsky R,Parkinson DB,Jessen KRdoi
10.1016/j.nbd.2006.06.006subject
Has Abstractpub_date
2006-10-01 00:00:00pages
159-69issue
1eissn
0969-9961issn
1095-953Xpii
S0969-9961(06)00143-4journal_volume
24pub_type
杂志文章abstract::Prion strains yield specific neuropathological features including spongiform degeneration and deposition patterns of pathological prion protein. Their invariant regional distribution, following variations in the infection route, has led to the proposal that prions replicate preferentially in defined neuro-anatomical a...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.09.010
更新日期:2011-01-01 00:00:00
abstract::Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability, and is the leading known single-gene cause of autism spectrum disorder. FXS patients display varied behavioural deficits that include mild to severe cognitive impairments in addition to mood disorders. Currently there is no cure fo...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.01.014
更新日期:2018-05-01 00:00:00
abstract::Malfunction of the ubiquitin-proteasome system has been implicated as a causal factor in the pathogenesis of aggregation-related disorders, e.g. Parkinson's disease. We show here that Transforming growth factor-beta 1 (TGF-beta), a multifunctional cytokine and trophic factor for dopaminergic (DAergic) neurons modulate...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.02.011
更新日期:2010-06-01 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:AIM:Recent studies revealed that pharmacological modulation of NAE-hydrolyzing acid amidase (NAAA) can be achieved with PEA oxazoline (PEA-OXA). Hence, the aim of the present work was to thoroughly evaluate the anti-inflammatory and neuroprotective effects of PEA-OXA in an experimental model of vascular dementia (VaD) ...
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::Although the incidence of seizures after a cerebrovascular event including intracerebral hemorrhage has been widely recognized, the present studies have demonstrated that generalized convulsive seizures can cause multifocal amygdaloallocortical hemorrhage and tissue necrosis, the origin of which remains to be establis...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.01.029
更新日期:2005-08-01 00:00:00
abstract::We identified a novel spontaneous mutant mouse showing motor symptoms that are similar to those of the dystonia musculorum (dt) mouse. The observations suggested that the mutant mice inherited the mild dt phenotype as an autosomal recessive trait. Linkage analysis showed that the causative gene was located near D1Mit3...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.09.016
更新日期:2016-12-01 00:00:00
abstract::Recently, we showed that oxidative stress activates the expression and activity of the beta-site AbetaPP-cleaving enzyme (BACE), an aspartyl protease responsible for the beta-secretase cleavage of AbetaPP. The identification of compounds able to prevent the induction of this event is an important goal of therapeutic s...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/s0969-9961(03)00131-1
更新日期:2003-11-01 00:00:00
abstract::Evidence of the gut microbiota influencing neurodegenerative diseases has been reported for several neural diseases. However, there is little insight regarding the relationship between the gut microbiota and prion disease. Here, using fecal samples of 12 prion-infected mice and 25 healthy controls, we analyzed the str...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.104704
更新日期:2020-02-01 00:00:00
abstract::Cellular mechanisms play a role in conversion of the normal prion protein PrP(C) to the disease-associated protein PrP(Sc). The cells provide not only PrP(C), but also still largely undefined factors required for efficient prion replication. Previously, we have observed that interference with ERK and p38-JNK MAP kinas...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.05.014
更新日期:2013-10-01 00:00:00
abstract::Giliosis is a hallmark of prion disease. A neurotoxic prion peptide (PrP106-126) induces astrocyte proliferation in the presence of microglia. This peptide also directly enhances microglial proliferation in culture. We have investigated this further to understand the method by which factors released by microglia and P...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.1998.0169
更新日期:1998-04-01 00:00:00
abstract::Cerebral ischemia activates endogenous neurogenesis in the subventricular zone (SVZ) and the dentate gyrus. Consecutively, SVZ-derived neural precursors migrate towards ischemic lesions. However, functional relevance of activated neurogenesis is limited by poor survival of new-born precursors. We therefore employed th...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2008.12.013
更新日期:2009-04-01 00:00:00
abstract::G-protein coupled receptor 3 (GPR3), GPR6, and GPR12 belong to a family of constitutively active Gs-coupled receptors that activate 3'-5'-cyclic adenosine monophosphate (cAMP) and are highly expressed in the brain. Among these receptors, the endogenous expression of GPR3 in cerebellar granule neurons (CGNs) is increas...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.04.007
更新日期:2014-08-01 00:00:00
abstract::The dystonias are comprised of a group of disorders that share common neurological abnormalities of involuntary twisting or repetitive movements and postures. The most common inherited primary dystonia is DYT1 dystonia, which is due to loss of a GAG codon in the TOR1A gene that encodes torsinA. Autopsy studies of brai...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.01.008
更新日期:2013-06-01 00:00:00
abstract::Patients with trisomy 21 [Down syndrome (DS)] progressively develop amyloid beta-protein (A beta) deposits and then other features of Alzheimer's disease (AD), apparently due to increased gene dosage and thus expression of the beta-amyloid precursor protein. Because the neuropathological phenotype in older DS subjects...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.1996.0003
更新日期:1996-02-01 00:00:00
abstract::Amyloid-β is a peptide released by synapses in physiological conditions and its pathological accumulation in brain structures necessary for memory processing represents a key toxic hallmark underlying Alzheimer's disease. The oligomeric form of Amyloid-β (Aβο) is now believed to represent the main Amyloid-β species af...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.07.001
更新日期:2018-10-01 00:00:00
abstract::Beta-amyloid (Abeta) deposition is one important pathological hallmark in Alzheimer's disease (AD). However, low levels of Abeta may modify critical endogenous protection systems before neurodegeneration occurs. We examined the time-course effect of sublethal concentrations of Abeta on total BDNF (panBDNF), BDNF trans...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2009.10.004
更新日期:2010-01-01 00:00:00
abstract::Oxidative stress and protein aggregation are biochemical hallmarks of Parkinson's disease (PD), a frequent sporadic late-onset degenerative disorder particularly of dopaminergic neurons in the substantia nigra, resulting in impaired spontaneous movement. PARK6 is a rare autosomal-recessively inherited disorder, mimick...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.10.007
更新日期:2007-02-01 00:00:00
abstract::Precursor cells in the adult dentate gyrus are a heterogeneous population. Astrocytic cell types with radial glia-like morphology and low proliferative activity have been distinguished from highly dividing subtypes expressing early neuronal properties. Recent evidence indicates that physiological stimuli predominantly...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.07.013
更新日期:2006-02-01 00:00:00
abstract::Microglia, a type of immune cell in the brain, are in a ramified status with branched processes in normal conditions. Upon pathological stimulation, microglia retract their processes and become activated. Searching methods to make the activated microglia return to ramified status would help cope with injuries induced ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2017.12.006
更新日期:2018-03-01 00:00:00
abstract::Mutations in the gene encoding the RNA-binding protein TDP-43 cause amyotrophic lateral sclerosis (ALS), clinically and pathologically indistinguishable from the majority of 'sporadic' cases of ALS, establishing altered TDP-43 function and distribution as a primary mechanism of neurodegeneration. Transgenic mouse mode...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.09.024
更新日期:2019-01-01 00:00:00
abstract::Experiments reported here were motivated by studies in both human epilepsy and animal models in which stunted dendritic arbors are observed. Our goal was to determine if chronic network hyperexcitability alters dendritic growth. Experiments were conducted in hippocampal slice cultures obtained from infant mice that ex...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2007.08.018
更新日期:2008-02-01 00:00:00
abstract::To study the role of Abeta amyloid deposits in the generation of cytoskeletal lesions, we have generated a transgenic mouse line coexpressing in the same neurons a wild-type human tau isoform (0N3R), a mutant form of APP (751SL) and a mutant form of PS1 (M146L). These mice developed early cerebral extracellular deposi...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2003.09.007
更新日期:2004-02-01 00:00:00
abstract::Stimulation of the nicotinic alpha7 acetylcholine receptor (nAChRalpha7) by nicotine or acetylcholine initiates the cholinergic anti-inflammatory pathway, a mechanism for neural inhibition of inflammation. The action of this pathway was initially discovered in animal models of endotoxemia and septic shock, and later d...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2009.03.010
更新日期:2009-07-01 00:00:00
abstract::Blood-brain barrier (BBB) disruption, mediated through matrix metalloproteinases (MMPs) and other mechanisms, is a critical event during ischemic stroke. Tissue plasminogen activator (tPA) is the only FDA-approved thrombolytic therapy for acute ischemic stroke, but the efficacy and safety of its therapeutic applicatio...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2010.03.008
更新日期:2010-06-01 00:00:00
abstract::Alpha-synuclein containing cellular inclusions are a hallmark of Parkinson Disease, Lewy Body Dementia, and Multiple System Atrophy. A genome wide expression screen was performed in C. elegans overexpressing both wild-type and A53T human alpha-synuclein. 433 genes were up- and 67 genes down-regulated by statistical an...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.12.021
更新日期:2006-06-01 00:00:00
abstract::To thoroughly understand the function and regulation of neurotransmitter systems in the brain, as well as the underlying disease mechanisms, it is important to comprehensively analyze the expression patterns of genes participating in such systems. Using functional annotated cDNA clones (FANTOM), we examined the gene e...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.01.021
更新日期:2005-08-01 00:00:00
abstract:PURPOSE:Generalized spike and wave discharges (SWD) are generated within the cortico-thalamo-cortical system. However the exact interactions between cortex and different thalamic nuclei needed for the generation and maintenance of SWD are still to be elucidated. This study aims to shed more light on these interactions ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.03.023
更新日期:2012-07-01 00:00:00
abstract::Recent work has demonstrated the importance of miRNAs in the pathogenesis of various brain disorders including the neurodegenerative disorder spinocerebellar ataxia (SCA). This review focuses on the role of miRNAs in the shared pathogenesis of the different SCA types. We examine the novel findings of a recent cell-typ...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2017.08.003
更新日期:2017-12-01 00:00:00
abstract::Several lines of evidence indicate that glutamate plays a crucial role in the initiation of seizures and their propagation; abnormal glutamate release causes synchronous firing of large populations of neurons, leading to seizures. In the present study, we investigated whether enhanced glutamate uptake by increased gli...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.03.032
更新日期:2012-08-01 00:00:00