Abstract：
:Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by the progressive loss of motor neurons, leading to profound weakness and eventual death of affected individuals. For the vast majority of patients with ALS, the etiology of the disorder is unknown, and although multiple clinical trials of various therapeutic agents have been undertaken, truly effective therapy is not currently available for the disease. The selection of treatments used in ALS clinical trials frequently has its basis in promising data obtained from experimental model systems in which the proposed agent has shown some effect in protecting motor neurons from a particular insult. The likelihood of a successful clinical outcome for a given treatment in ALS would therefore depend on two principal factors, including the similarity of the model to the disease and the biologic action of the potential therapeutic agent. Partly because early experimental models of ALS failed to replicate the disease process, treatment success in these models did not carry over into human trials. Recently, however, a variety of newer model systems have been developed and utilized to investigate motor neuron degeneration as related to ALS. For example, in this issue, Corse et al. use a rat spinal cord organotypic slice subjected to glutamate excitotoxicity as a model system to test the effectiveness of neurotrophic factors in preventing motor neuron degeneration. This review will assess the strengths and weaknesses of differing ALS model systems that have been used to preclinically test potential drug efficacy in ALS.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Elliott JLdoi
10.1006/nbdi.1999.0266keywords:
subject
Has Abstractpub_date
1999-10-01 00:00:00pages
310-20issue
5eissn
0969-9961issn
1095-953Xpii
S0969-9961(99)90266-8journal_volume
6pub_type
杂志文章,评审abstract：:Butyrylcholinesterase (BChE) genotypes and protein (BuChE) activity, especially in combination with Apolipoprotein E4 (ApoE4), have been investigated as risk factors for developing Alzheimer disease (AD) and may be associated with the rate of progression of cognitive decline. Despite similar pathologic (e.g. amyloid d...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2009.05.014
更新日期：2009-08-01 00:00:00
abstract：:No single-omic approach completely elucidates the multitude of alterations taking place in Alzheimer's disease (AD). Here, we coupled transcriptomic and phosphoproteomic approaches to determine the temporal sequence of changes in mRNA, protein, and phosphopeptide expression levels from human temporal cortical samples,...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.12.009
更新日期：2019-04-01 00:00:00
abstract：:Over 1250 mutations in SCN1A, the Nav1.1 voltage-gated sodium channel gene, are associated with seizure disorders including GEFS+. To evaluate how a specific mutation, independent of genetic background, causes seizure activity we generated two pairs of isogenic human iPSC lines by CRISPR/Cas9 gene editing. One pair is...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2019.104627
更新日期：2020-02-01 00:00:00
abstract：:Pathological high-frequency oscillations (HFOs), specifically fast ripples (FRs, >250 Hz), are pathognomonic of an active epileptogenic zone. However, the origin of FRs remains unknown. Here we explored the correlation between FRs recorded with intraoperative pre-resection electrocorticography (ECoG) and spontaneous s...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2019.104618
更新日期：2020-02-01 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：:The unfolded protein response (UPR) monitors the folding environment within the endoplasmic reticulum (ER). Accumulation of misfolded proteins within the ER activates the UPR resulting in the execution of adaptive or non-adaptive signaling pathways. α-Synuclein (α-syn) whose accumulation and aggregation define the pat...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2015.02.005
更新日期：2015-04-01 00:00:00
abstract：:Mitochondrial dysfunction plays an important role in the pathogenesis of neurodegenerative diseases, numerous other disease states and senescence. The ability to monitor reactive oxygen species (ROS) within tissues and over time in animal model systems is of significant research value. Recently, redox-sensitive fluore...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2011.08.022
更新日期：2012-01-01 00:00:00
abstract：:Mutations in the gene for DJ-1 have been associated with early-onset autosomal recessive parkinsonism. Previous studies of null DJ-1 mice have shown alterations in striatal dopamine (DA) transmission with no DAergic cell loss. Here we characterize a new line of DJ-1-deficient mice. A subtle locomotor deficit was prese...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2007.03.014
更新日期：2007-08-01 00:00:00
abstract：:Aging is the strongest risk factor for metabolic, vascular and neurodegenerative diseases. Aging alone is associated with a gradual decline of cognitive and motor functions. Considering an increasing elderly population in the last century, understanding the cellular and molecular mechanisms contributing to brain aging...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2020.105008
更新日期：2020-09-01 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：:Parkinson's Disease (PD) and Multiple System Atrophy (MSA) are neurodegenerative diseases characterized neuropathologically by alpha-synuclein accumulation in brain cells. This accumulation is hypothesized to contribute to constitutive neuroinflammation, and to participate in the neurodegeneration. Cytokines, which ar...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2017.07.014
更新日期：2017-10-01 00:00:00
abstract：:Loss-of-function mutations in the parkin-encoding PARK2 gene are a frequent cause of young-onset, autosomal recessive Parkinson's disease (PD). Parkin knockout mice have no nigro-striatal neuronal loss but exhibit abnormalities of striatal dopamine transmission and cortico-striatal synaptic function. How these predege...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2020.104737
更新日期：2020-04-01 00:00:00
abstract：:Somatosensation plays a critical role in the dexterous manipulation of objects, in emotional communication, and in the embodiment of our limbs. For upper-limb neuroprostheses to be adopted by prospective users, prosthetic limbs will thus need to provide sensory information about the position of the limb in space and a...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2014.08.029
更新日期：2015-11-01 00:00:00
abstract：:Environmental toxicants and, in particular, pesticides have been implicated as risk factors in Parkinson's disease (PD). The purpose of this study was to determine if selective nigrostriatal degeneration could be reproduced by systemic exposure of mice to the widely used herbicide paraquat. Repeated intraperitoneal pa...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1006/nbdi.2002.0507
更新日期：2002-07-01 00:00:00
abstract：:Spinal muscular atrophy (SMA), a genetic neurodegenerative disorder, is caused by mutations or deletions in the survival of motor neuron 1 (SMN1) gene that result in SMN deficiency. SMN deficiency impairs microtubule networks in Smn-deficient cells and in SMA-like motor neuron cultures. Microtubule defects can be rest...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2012.11.015
更新日期：2013-04-01 00:00:00
abstract：:There is clear evidence that an inflammatory reaction is mounted within the CNS following trauma, stroke, infection and seizures, thus augmenting brain damage. Furthermore, chronic inflammation of the CNS is implicated in many neurodegenerative disorders. However, the effects of products of inflammation on neuronal ce...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2005.11.006
更新日期：2006-05-01 00:00:00
abstract：:This paper presents a novel model of tremor in Parkinson's disease (PD) based on extensive literature review as well as novel results stemming from functional stereotactic neurosurgery for the alleviation of tremor in PD. Specifically, evidence that suggests the basal ganglia induces PD tremor via excessive inhibitory...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2015.10.009
更新日期：2016-01-01 00:00:00
abstract：:Adult-onset hypothyroidism is associated with neurological changes such as cognitive dysfunction and impaired learning, which may be related to alterations of synaptic plasticity. We investigate the consequence of adult-onset hypothyroidism on thyroid-mediated transcription events in striatal synaptic plasticity, and ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2008.05.015
更新日期：2008-09-01 00:00:00
abstract：:The molecular mechanisms of major mental illnesses, such as schizophrenia and bipolar disorder, are unclear. To address this fundamental question, many groups have studied molecular expression profiles in postmortem brains and other tissues from patients compared with those from normal controls. Development of unbiase...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2011.08.025
更新日期：2012-01-01 00:00:00
abstract：:Microglia and macrophages express the alpha(M)/beta(2) integrin complement-receptor-3 (CR3/MAC-1; CD11b/CD18) and scavenger-receptor-AI/II (SRAI/II). Both can mediate myelin phagocytosis. We document that CR3/MAC-1 mediated myelin phagocytosis in microglia is modulated by complement and anti-CR3/MAC-1 mAbs. Complement...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/s0969-9961(02)00008-6
更新日期：2003-02-01 00:00:00
abstract：:Glutathione (GSH) is an important neuroprotective molecule in the brain. The strategy to increase neuronal GSH level is a promising approach to the treatment of neurodegenerative diseases. However, the regulatory mechanism by which neuron-specific GSH synthesis is facilitated remains elusive. Glutamate transporter-ass...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2011.12.016
更新日期：2012-03-01 00:00:00
abstract：:The disruption of the blood-spinal cord barrier (BSCB) by matrix metalloprotease (MMP) activation is a detrimental event that leads to blood cell infiltration, inflammation, and apoptosis, thereby contributing to permanent neurological disability after spinal cord injury (SCI). However, the molecular mechanisms underl...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2016.07.015
更新日期：2016-11-01 00:00:00
abstract：:Fetal alcohol exposure causes severe neuropsychiatric problems, but mechanisms of the ethanol-associated changes in central nervous system development are unclear. In vivo, ethanol's interaction with N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid type A (GABA(A)) receptors may cause increased apoptosis in the...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1006/nbdi.2002.0523
更新日期：2002-08-01 00:00:00
abstract：:Heterozygous in frame duplications of the PHOX2B gene, leading to polyalanine (polyAla) expansions ranging from +5 to +13 residues of a 20-alanine stretch, have been identified in the vast majority of patients affected with Congenital Central Hypoventilation Syndrome (CCHS), a rare neurocristopathy characterized by ab...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2011.09.007
更新日期：2012-01-01 00:00:00
abstract：:Alzheimer's disease (AD) involves changes in both lipid and RNA metabolism, but it remained unknown if these differences associate with AD's cognition and/or post-mortem neuropathology indices. Here, we report RNA-sequencing evidence of inter-related associations between lipid processing, cognition level, and AD neuro...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2017.06.008
更新日期：2017-10-01 00:00:00
abstract：:An important aspect of Huntington's disease (HD) pathogenesis which may have important therapeutic implications is that the cellular events leading to cell death may be different in cortical and striatal neurons. In the present study, we characterized cellular changes in cortical and striatal neurons treated with the ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2003.09.013
更新日期：2004-02-01 00:00:00
abstract：:Fragile X Syndrome (FXS) is a heritable form of mental retardation caused by a non-coding trinucleotide expansion of the FMR1 gene leading to loss of expression of this RNA binding protein. Mutations in this gene are strongly linked to enhanced Group I metabotropic glutamate receptor (mGluR) signaling. A recent report...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2013.04.002
更新日期：2013-08-01 00:00:00
abstract：:Markers of the kynurenine pathway were studied in postmortem frontal cortex obtained from individuals with schizophrenia and controls. Quantitative endpoint RT-PCR was used to measure mRNA transcripts. Of the two enzymes capable of catalyzing the first step in the pathway, tryptophan 2,3-dioxygenase (TDO2) and indolea...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2003.12.015
更新日期：2004-04-01 00:00:00
abstract：:We recently reported evidence for disturbed synaptic versus extrasynaptic NMDAR transmission in the early pathogenesis of Huntington's disease (HD), a late-onset neurodegenerative disorder caused by CAG repeat expansion in the gene encoding huntingtin. Studies in glutamatergic cells indicate that synaptic NMDAR transm...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2012.05.013
更新日期：2012-10-01 00:00:00
abstract：:Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat. Its length can be used to estimate the time of clinical diagnosis, which is defined by overt motor symptoms. Non-motor symptoms begin before motor onset, and involve changes in hypothalamus-regulated functions such as sleep...
journal_title：Neurobiology of disease
pub_type： 杂志文章,多中心研究
doi：10.1016/j.nbd.2010.07.013
更新日期：2010-12-01 00:00:00
