Abstract:
:Small-molecule inhibitors of neurofibrillary lesion formation may have utility for treatment of Alzheimer's disease and certain forms of frontotemporal lobar degeneration. These lesions are composed largely of tau protein, which aggregates to form intracellular fibrils in affected neurons. Previously it was shown that chronic overexpression of human tau protein within identified neurons (anterior bulbar cells) of the sea lamprey induced a phenotype-resembling tauopathic neurodegeneration, including the formation of tau filaments, fragmentation of dendritic arbors, and eventual cell death. Development of this neurodegenerative phenotype was blocked by chronic administration of a benzothiazole derivative termed N3 ((E)-2-[[4-(dimethylamino)phenyl]azo]-6-methoxybenzothiazole) to lamprey aquaria. Here we examined the mechanism of action of N3 and an alkene analog termed N4 ((E)-2-[2-[4-(dimethylamino)phenyl]ethenyl]-6-methoxybenzothiazole) in vitro and in the lamprey model. Results showed that although both compounds entered the lamprey central nervous system, only N3 arrested tauopathy. On the basis of in vitro aggregation assays, neither compound was capable of directly inhibiting tau filament formation. However, N3, but not N4, was capable of partially antagonizing the binding of Thioflavin S to synthetic tau filaments. The results suggest that occupancy of N3-binding sites on nascent tau filaments may significantly retard the progressive degeneration accompanying tau overexpression in lamprey.
journal_name
Neurotox Resjournal_title
Neurotoxicity researchauthors
Honson NS,Jensen JR,Abraha A,Hall GF,Kuret Jdoi
10.1007/s12640-009-9028-ysubject
Has Abstractpub_date
2009-04-01 00:00:00pages
274-83issue
3eissn
1029-8428issn
1476-3524journal_volume
15pub_type
杂志文章abstract::Microglial activation and subsequent release of toxic pro-inflammatory factors are believed to play an important role in neuronal cell death associated with Parkinson's disease (PD). Compounds that inhibit microglia activation and suppress pro-inflammatory factor release have been reported to have neuroprotective effe...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-012-9328-5
更新日期:2013-02-01 00:00:00
abstract::Patients scheduled for cochlear implantation often retain residual hearing in the low frequencies. Unfortunately, some patients lose their residual hearing following implantation and the reasons for this are not well understood. Evidence suggests that electrotoxicity could be one of the factors responsible for this la...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00017-x
更新日期:2019-07-01 00:00:00
abstract::Melamine is an industrial chemical that can cause central nervous system disorders including excitotoxicity and cognitive impairment. Its illegal use in powdered baby formula was the focus of a milk scandal in China in 2008. One of our previous studies showed that melamine impaired glutamatergic transmission in rat hi...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-015-9570-8
更新日期:2016-01-01 00:00:00
abstract::Organophosphate (OP) poisoning is associated with long-lasting neurological damage, which is attributed mainly to the excessive levels of glutamate caused by the intoxication. Glutamate toxicity, however, is not specific to OP poisoning, and is linked to propagation of damage in both acute and chronic neurodegenerativ...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/s12640-013-9388-1
更新日期:2013-08-01 00:00:00
abstract::Maillard reactions have been explored by food chemists for many years. It is only recently that the advanced glycation end products (AGEs), the end products of the Maillard reaction, have been detected in a wide variety of diseases such as diabetes, atherosclerosis, cataractogenesis, Parkinson disease and Alzheimer di...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1080/1029840290007321
更新日期:2002-05-01 00:00:00
abstract::Local anesthetics effectively block and relieve pain, but with a relatively short duration of action, limiting its analgesic effectiveness. Therefore, a long-acting local anesthetic would improve the management of pain, but no such agent is yet available for clinical use. The aim of this study is to evaluate the poten...
journal_title:Neurotoxicity research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s12640-009-9092-3
更新日期:2009-11-01 00:00:00
abstract::Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-016-9599-3
更新日期:2016-05-01 00:00:00
abstract::Huntington's disease (HD) is a fatal autosomal dominantly inherited brain disease caused by excessively expanded CAG repeats in gene which encodes huntingtin protein. These abnormally encoded huntingtin proteins and their truncated fragments result in disruption of cellular quality mechanism ultimately triggering neur...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/s12640-019-00087-x
更新日期:2019-10-01 00:00:00
abstract::The present study shows that intranigral injection of dicoumarol, a DT-diaphorase inhibitor, potentiates the neurotoxic effect of salsolinol (salsolinol 1.25 nmoles plus dicoumarol 2 nmoles; in 2 microl). Rats treated with dicoumarol plus salsolinol presented a characteristic contralateral rotational behaviour when th...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033183
更新日期:2004-01-01 00:00:00
abstract::Edaravone is a novel free radical scavenger that is clinically employed in patients with acute cerebral infarction, but has not previously been used to treat traumatic brain injury (TBI). In this study, we investigated the effect of edaravone administration on rat TBI. In particular, we used immunohistochemistry to mo...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-009-9081-6
更新日期:2009-11-01 00:00:00
abstract::Intracerebral or intraperitoneal injections of brain extracts from the Alzheimer's disease patients result in the acceleration of cerebral β-amyloidosis in transgenic mice. Earlier, we have found that intravenous injections of synthetic full-length amyloid-β (Aβ) comprising the isomerized Asp7 trigger cerebral β-amylo...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-016-9603-y
更新日期:2016-05-01 00:00:00
abstract::In the context of our current knowledge about schizophrenia, heuristic models of psychiatric disorders may be used to test the plausibility of theories developed on the basis of new emerging biological findings, explore mechanisms of schizophrenia-like phenomena, and develop potential new treatments. In a series of st...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1080/1029842021000022089
更新日期:2002-08-01 00:00:00
abstract::Inflammation can cause memory impairment. In the present study, the effect of carvacrol on brain tissue inflammation and oxidative stress as well as learning and memory in lipopolysaccharide (LPS)-challenged rats was evaluated. The animals were grouped and treated: (1) control which received vehicle instead of LPS and...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00144-5
更新日期:2020-04-01 00:00:00
abstract::Organophosphates (OPs) inhibit cholinesterase and hyperactivate the acetylcholinergic nervous system in the brain, causing motor disorders (e.g., tremor and seizures). Here, we performed behavioral and immunohistochemical studies in mice and rats to investigate the tremorgenic mechanism of paraoxon, an active metaboli...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-0007-7
更新日期:2019-04-01 00:00:00
abstract::Non-motor symptoms are increasingly identified to present clinical and diagnostic importance for Parkinson's disease (PD). The multifactorial origin of pain in PD makes this symptom of great complexity. The dopamine precursor, L-DOPA (L-3,4-dihydroxyphenylalanine), the classic therapy for PD, seems to be effective in ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-018-9896-0
更新日期:2018-11-01 00:00:00
abstract::Cultured rat fibroblasts, monkey kidney tumor cells (line Vero) and murine neuroblastoma cells were exposed to dopamine or dopaminochrome in the presence and absence of ascorbic acid. Ascorbic acid is able to potentiate the toxicity of both dopamine and dopaminochrome for all the tested cells. The toxicity of dopamino...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033278
更新日期:1999-12-01 00:00:00
abstract::The level of acetylcholine, a neurotransmitter essential for processing memory and learning, is lower in the brains of patients with Alzheimer's disease due to the higher concentration of the enzyme acetylcholinesterase. The main compounds used for Alzheimer's treatment are acetylcholinesterase inhibitors. Quercetin c...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00142-7
更新日期:2020-04-01 00:00:00
abstract::The study shows effects of the nonselective adenosine A1/A2A receptor antagonist caffeine and the selective A2A receptor antagonist KW6002 on LPS-induced changes in the extracellular levels of dopamine (DA), glutamate, adenosine, hydroxyl radical, and A2A receptor density in the rat striatum. Intrastriatal LPS (10 μg)...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-012-9372-1
更新日期:2013-07-01 00:00:00
abstract::Prenatal glucocorticoid (GC) overexposure impacts fetal hippocampal neural stem cells (NSCs) and increases the risk for relative cognitive and mood disorders in offspring. However, the precise underlying mechanisms remain elusive. Here, we treated mouse hippocampal NSCs with dexamethasone (DEX) in vitro and found that...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-020-00294-x
更新日期:2020-10-06 00:00:00
abstract::Synthetic cathinones appeared on the market in the 2000s as new psychoactive substances and gained significant prevalence among drug abusers. Cathinones produce psychostimulant and empathogenic effects by enhancing dopaminergic, noradrenergic, and serotoninergic neurotransmission in the brain, and those which potently...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-021-00329-x
更新日期:2021-01-11 00:00:00
abstract::Cocaine was previously shown to act at the Sigma1R which is a target for counteracting cocaine actions. It therefore becomes of interest to test if the monoamine stabilizer (-) OSU-6162 (OSU-6162) with a nanomolar affinity for the Sigma1R can acutely modulate in low doses the effects of cocaine self-administration. In...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00134-7
更新日期:2020-02-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the progressive degeneration of brain and spinal cord motor neurons. Ubiquitin-proteasome system (UPS) dysfunction and oxidative stress have been implicated in ALS pathogenesis. However, it is unknown whether the defects in thes...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-015-9532-1
更新日期:2015-08-01 00:00:00
abstract::The 1,2,3,4-tetrahydroisoquinolines (TIQs) are compounds frequently described as alkaloids that can be found in the human body fluids and/or tissues including the brain. In most circumstances, TIQs may be originated as a consequence of reactions, known as Pictet-Spengler condensations, between biogenic amines and elec...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/s12640-019-00051-9
更新日期:2019-11-01 00:00:00
abstract::The sigma1 receptor (σ1R) is a chaperone protein residing at mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), where it modulates Ca2+ exchange between the ER and mitochondria by interacting with inositol-1,4,5 trisphosphate receptors (IP3Rs). The σ1R is highly expressed in the central nervous syste...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-017-9838-2
更新日期:2019-01-01 00:00:00
abstract::Alcoholism is associated with a higher incidence of smoking. In addition to the stimulatory effects of both ethanol and nicotine on the mesolimbic reward pathway, nicotine's ability to counteract some of the adverse effects of ethanol (e.g. ataxia) may be a powerful incentive for alcohol consumers to increase their to...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033151
更新日期:2003-01-01 00:00:00
abstract::L-3,4-dihydroxyphenylalanine (L-dopa) remains the most effective drug for therapy of Parkinson's disease (PD); however, long-term use of it causes serious side effects. L-dopa-induced dyskinesia (LID) has consistently been related to L-dopa-derived excessive dopamine release, but the mechanisms have not been addressed...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-016-9686-5
更新日期:2017-04-01 00:00:00
abstract::In multicellular organisms, all the cells are genetically identical but turn genes on or off at the right time to promote differentiation into specific cell types. The regulation of higher-order chromatin structure is essential for genome-wide reprogramming and for tissue-specific patterns of gene expression. The comp...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/s12640-014-9497-5
更新日期:2015-01-01 00:00:00
abstract::Curcumin, a natural polyphenolic compound, has long been known as an anti-tumour and anti-inflammatory compound; although, the common mechanism through which it exhibits such properties are remains unclear. Recently, we reported that the curcumin-induced apoptosis is mediated through the impairment of ubiquitin protea...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033305
更新日期:2006-01-01 00:00:00
abstract::There is a long-standing debate about whether rats have what could be considered a prefrontal cortex (PFC) and, if they do, what its primate homologue is. Anatomical evidence supports the view that the rat medial PFC is related to both the primate anterior cingulate cortex (ACC) and the dorsolateral PFC. Functionally ...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033814
更新日期:2008-10-01 00:00:00
abstract::Rats lesioned shortly after birth with 6-hydroxydopamine (6-OHDA; 134 μg icv) represent a near-ideal model of severe Parkinson's disease because of the near-total destruction of nigrostriatal dopaminergic fibers. There are scarce data that in Parkinson's disease, activity of the central histaminergic system is increas...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-011-9251-1
更新日期:2012-02-01 00:00:00