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-DArgic neurons, exhibiting sensitivity at lower concentrations, evident by morphological and neurotransmitter uptake studies. BH4-exposed DArgic neurons showed (1) increased TUNEL staining and activated caspase-3 immunoreactivity, indicative of apoptotic death; (2) mitochondrial membrane potential loss and increased cytosolic cytochrome c, suggesting mitochondrial dysfunction; (3) increased level of oxidized proteins and protection by antioxidants, indicative of oxidative stress; and (4) increased ubiquitin immunoreactivity, suggesting alteration of protein degradation pattern. Percent of cells positive for these parameters were much higher for DArgic neurons, demonstrating preferential vulnerability. Therefore, the DArgic neuronal damage induced by BH4, the molecule synthesized and readily upregulated in DArgic neurons and activated microglia, suggests physiological relevance to the pathogenesis of PD.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Lee SY,Moon Y,Hee Choi D,Jin Choi H,Hwang Odoi
10.1016/j.nbd.2006.08.024subject
Has Abstractpub_date
2007-01-01 00:00:00pages
112-20issue
1eissn
0969-9961issn
1095-953Xpii
S0969-9961(06)00217-8journal_volume
25pub_type
杂志文章abstract::Prion diseases are disorders of protein conformation that produce neurodegeneration in humans and animals. Studies of transgenic (Tg) mice indicate that a factor designated protein X is involved in the conversion of the normal cellular prion protein (PrPC) into the scrapie isoform (PrPSc); protein X appears to interac...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.1997.0130
更新日期:1997-01-01 00:00:00
abstract::Rubrospinal neurons (RSNs) undergo marked atrophy after cervical axotomy. This progressive atrophy may impair the regenerative capacity of RSNs in response to repair strategies that are targeted to promote rubrospinal tract regeneration. Here, we investigated whether we could achieve long-term rescue of RSNs from lesi...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2003.11.018
更新日期:2004-03-01 00:00:00
abstract::Mutations in LRRK2 are the most common genetic cause of Parkinson's disease (PD). The most prevalent LRRK2 mutation is the G2019S coding change, located in the kinase domain of this complex multi-domain protein. The majority of G2019S autopsy cases feature typical Lewy Body pathology with a clinical phenotype almost i...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.05.017
更新日期:2013-10-01 00:00:00
abstract::The pathophysiology of Parkinson's disease (PD) and of L-DOPA-induced dyskinesia (LID) is associated with dysfunctional neuronal activity in several nuclei of the basal ganglia. Moreover, high levels of oscillatory activity and synchronization have also been described in both intra- and inter-basal ganglia nuclei and ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.02.003
更新日期:2016-05-01 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::This article reviews three concepts related to implantable brain computer interface (BCI) devices being designed for human use: neural signal extraction primarily for motor commands, signal insertion to restore sensation, and technological challenges that remain. A significant body of literature has occurred over the ...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2009.12.007
更新日期:2010-06-01 00:00:00
abstract::Several reports indicate that the activity of the hypothalamic–pituitary–adrenal axis (HPA) is increased after a brain insult and that its down-regulation can improve detrimental outcomes associated with ischemic brain injuries.Granulocyte-colony stimulating factor (G-CSF) is a neuroprotective drug shown in the naïve ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.03.021
更新日期:2012-07-01 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::Amyotrophic lateral sclerosis (ALS) is a fatal disease of unknown etiology. Mutations in copper/zinc superoxide dismutase (SOD1) are the most commonly associated genetic abnormality. Given that SOD1 is ubiquitously expressed, the exclusive vulnerability of motor neurons is one of the most puzzling issues in ALS resear...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.03.007
更新日期:2006-08-01 00:00:00
abstract::Parkinson disease (PD) is a systemic disease with variegated non-motor deficits and neurological symptoms, including impaired olfaction, autonomic failure, cognitive impairment and psychiatric symptoms, in addition to the classical motor symptoms. Many non-motor symptoms appear before or in parallel with motor deficit...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2011.10.019
更新日期:2012-06-01 00:00:00
abstract::The genetic associations with the pathological features of AD are diverse: A rapidly growing number of mutations in presenilin 1 and 2 on chromosomes 14 and 1, respectively, are found in many early-onset FAD patients (Lendon et al., 1997). In addition, beta PP mutations are found in a small percentage of early-onset F...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1006/nbdi.1997.0147
更新日期:1997-01-01 00:00:00
abstract::Pathological oxygen deprivation inhibits prolyl hydroxylase (PHD) activity and stimulates a protective cellular oxygen-sensing response in part through the stabilization and activation of the Hypoxia Inducible Factor (HIF) 1α transcription factor. The present investigation tested the therapeutic potential of enhanced ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2011.10.020
更新日期:2012-02-01 00:00:00
abstract::Amyloid beta-peptide (Abeta) containing plaques and neurofibrillary tangles (NFT) are the two major histopathological hallmarks of Alzheimer's disease (AD). According to the amyloid cascade hypothesis, deposition of Abeta is an initial and essential step in the pathogenesis of AD, and formation of NFT has been propose...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.10.002
更新日期:2006-04-01 00:00:00
abstract::Gephyrin is a postsynaptic scaffolding protein, essential for the clustering of glycine and γ-aminobutyric acid type-A receptors (GABAARs) at inhibitory synapses. An impairment of GABAergic synaptic inhibition represents a key pathway of epileptogenesis. Recently, exonic microdeletions in the gephyrin (GPHN) gene have...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.02.001
更新日期:2014-07-01 00:00:00
abstract::Our previous studies demonstrated that the psychostimulant methamphetamine (MA) and the human immunodeficiency virus-1 (HIV-1) protein Tat interacted to cause enhanced dopaminergic neurotoxicity. The present study examined whether tumor necrosis factor-alpha (TNF-alpha) mediates the interaction between Tat and MA. In ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.05.005
更新日期:2006-09-01 00:00:00
abstract::Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that results in motor, cognitive and psychiatric abnormalities. Dysfunction in neuronal processing between the cortex and the basal ganglia is fundamental to the onset and progression of the HD phenotype. The corticosubthalamic hyperdirect p...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2015.03.006
更新日期:2015-06-01 00:00:00
abstract::Astrocytes are abundant neuron-supporting glial cells that harbor a powerful arsenal of neuroprotective antioxidative molecules and neurotrophic factors. Here we examined whether enrichment with healthy striatal astrocytes can provide neuroprotection against progressive dopaminergic neurodegeneration. Serotonin 1A (5-...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.08.003
更新日期:2013-11-01 00:00:00
abstract::GDAP1 is an outer mitochondrial membrane protein that acts as a regulator of mitochondrial dynamics. Mutations of the GDAP1 gene cause Charcot-Marie-Tooth (CMT) neuropathy. We show that GDAP1 interacts with the vesicle-organelle trafficking proteins RAB6B and caytaxin, which suggests that GDAP1 may participate in the ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.03.010
更新日期:2013-07-01 00:00:00
abstract::Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by dyskinesia, cognitive impairment and emotional disturbances, presenting progressive neurodegeneration in the striatum and intracellular mutant Huntingtin (mHTT) aggregates in various areas of the brain. Recombinant Adeno Associated V...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2015.11.019
更新日期:2016-02-01 00:00:00
abstract::Inhibition of mitochondrial axonal trafficking by amyloid beta (Aβ) peptides has been implicated in early pathophysiology of Alzheimer's Disease (AD). Yet, it remains unclear whether the loss of motility inevitably induces the loss of mitochondrial function, and whether restoration of axonal trafficking represents a v...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.02.003
更新日期:2018-06-01 00:00:00
abstract::Background While significant advances have been made in uncovering the aetiology of Alzheimer's disease and related dementias at the genetic level, molecular events at the epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) and their associated RNA modifications ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2020.105058
更新日期:2020-11-01 00:00:00
abstract::In amyotrophic lateral sclerosis (ALS), the exogenous temporal triggers that result in initial motor neuron death are not understood. Overactivation and consequent accelerated loss of vulnerable motor neurons is one theory of disease initiation. The vulnerability of motor neurons in response to chronic peripheral nerv...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.03.021
更新日期:2010-09-01 00:00:00
abstract::Aggregation of α-synuclein (α-syn) is neuropathologically and genetically linked to Parkinson's disease (PD). Since stereotypic cell-to-cell spreading of α-syn pathology is believed to contribute to disease progression, immunotherapy with antibodies directed against α-syn is considered a promising therapeutic approach...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.10.016
更新日期:2019-04-01 00:00:00
abstract::Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (FALS), and approximately 25% of FALS cases are caused by mutations in superoxide dismutase-1 (SOD1). Mutant (MT) SOD1 kills motor neurons because of the mutant protein's toxicity; however, the basis for toxicity is unknown. We electroporated ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.07.006
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Epidemiological studies suggest that the risk of neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia is increased by prenatal exposure to viral or bacterial infection during pregnancy. It is still unclear how activation of the maternal immune response interacts with underlyi...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.01.025
更新日期:2019-05-01 00:00:00
abstract::NAP (NAPVSIPQ) provides broad neuroprotection through microtubule interaction. Here, NAP was investigated for neuroprotection in an in vivo tauopathy model. Transgenic mice (2-month-old) that express the human double mutant tau protein [P301S;K257T] fused to the tau promoter, were subjected to daily intranasal drug tr...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2009.02.011
更新日期:2009-05-01 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::Mental illness is the leading cause of disability worldwide. We are only just beginning to reveal and comprehend the complex interaction that exists between the genetic makeup of an organism and the potential modifying effect of the environment in which it lives, and how this translates into mediating susceptibility t...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2012.04.003
更新日期:2013-09-01 00:00:00
abstract::Presenilin 1 (PSEN1) mutations are the main cause of autosomal dominant Early-onset Alzheimer Disease (EOAD). Among them, deletions of exon 9 have been reported to be associated with a phenotype of spastic paraparesis. Using exome data from a large sample of 522 EOAD cases and 584 controls to search for genomic copy-n...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2017.04.020
更新日期:2017-08-01 00:00:00
abstract::Motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is a form of apoptosis, but the mechanisms for this neuronal cell death are not known. We evaluated whether motor neuron degeneration in ALS is associated with changes in the levels and function of the apoptosis regulating protein p53. The protein levels...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.2000.0314
更新日期:2000-12-01 00:00:00