Abstract:
:Parkinson's disease (PD) is the second most familiar, progressive and movement-related neurodegenerative disorder after Alzheimer disease. This study aimed to decipher the role of autophagy in cypermethrin-induced Parkinsonism, an animal model of PD. Indicators of autophagy [expression of beclin 1, autophagy-related protein 12 (Atg 12), unc-51 like autophagy activating kinase 1 (Ulk 1), p62 and lysosome-associated membrane protein 2 (LAMP 2) and conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3) I to II], signalling cascade [phosphorylated (p) 5' adenosine monophosphate-activated protein kinase (p-AMPK), sirtuin 1 (Sirt 1), phosphorylated-mammalian target of rapamycin (p-mTOR), tuberous sclerosis complex 2 (TSC 2), p317Ulk 1 and p757Ulk 1 levels] and lysosome morphology were assessed in control and cypermethrin-treated rat model of PD. Autophagy markers were also measured in cypermethrin-treated neuroblastoma cells in the presence of 3-methyl adenine, a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) class III inhibitor; vinblastine, an autophagosome elongation inhibitor; bafilomycin A1, an autophagolysosome and lysosome fusion/abnormal acidification inhibitor or torin 1, a mechanistic target of rapamycin inhibitor. Cypermethrin reduced LAMP 2 and increased p-AMPK and Sirt 1 without causing any change in other signalling proteins. 3-Methyl adenine did not change LC3 conversion; vinblastine and bafilomycin A1 decreased LAMP 2 expression in controls. While cypermethrin increased LC3 conversion in the presence of 3-methyl adenine, LAMP 2 reduction was more pronounced in vinblastine and bafilomycin A1-treated cells. Torin 1 normalized the expression of LAMP 2 without any change in other autophagy markers. Results demonstrate that albeit cypermethrin activates autophagosome formation, it reduces LAMP 2 expression and lysosome quality leading to autophagy inhibition.
journal_name
Neurotox Resjournal_title
Neurotoxicity researchauthors
Mishra AK,Mishra S,Rajput C,Ur Rasheed MS,Patel DK,Singh MPdoi
10.1007/s12640-017-9800-3subject
Has Abstractpub_date
2018-02-01 00:00:00pages
377-387issue
2eissn
1029-8428issn
1476-3524pii
10.1007/s12640-017-9800-3journal_volume
33pub_type
杂志文章abstract:BACKGROUND:Monoclonal antibodies (MAbs) against neurotoxin of Clostridium tetani are considered as a novel source of immunoglobulins for passive immunotherapy of tetanus. Toxin neutralization is classically attributed to the Fab and F(ab')2 fragments of antibodies. Herein, we generated Fab and F(ab')2 fragments of thre...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00124-9
更新日期:2020-03-01 00:00:00
abstract::Accumulating data support axonal degeneration as the major determinant of irreversible neurological disability in patients with multiple sclerosis (MS). The extent of axonal injury correlates with the degree of inflammation in active MS lesions and occurs at early stages of disease, indicating that inflammatory demyel...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033380
更新日期:2003-01-01 00:00:00
abstract::Several studies investigated the prognostic role of copeptin in stroke. The aim of this study is to assess copeptin levels in serum, and investigate their associations with risk of recurrent stroke in a 1-year follow-up study in patients with ischemic stroke. In this post hoc analysis, serum levels of copeptin and NIH...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-017-9754-5
更新日期:2017-10-01 00:00:00
abstract::During neonatal life, offspring can be affected by toxic agents either by transfer via mother's milk or by direct exposure. In many mammalian species the perinatal period is characterized by a rapid development of the brain - "the brain growth spurt" (BGS). This period in the development of the mammalian brain is asso...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033229
更新日期:2001-01-01 00:00:00
abstract::Tissue accumulation of L-2-hydroxyglutaric acid (L-2-HG) is the biochemical hallmark of L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic inherited disease characterized by neurological symptoms and brain white matter abnormalities whose pathogenesis is not yet well established. L-2-HG was intracerebrally ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-018-9874-6
更新日期:2018-04-01 00:00:00
abstract::Botulinum neurotoxins (BoNTs), the causative agents of botulism, are potent inhibitors of neurotransmitter release from motor neurons. There are currently no drugs to treat BoNT intoxication after the onset of the disease symptoms. In this study, we explored how modulation of key host pathways affects the process of B...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-015-9526-z
更新日期:2015-05-01 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::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::U373MG cells are able to take up aminochrome that induces glutathione transferase M2-2 (GSTM2) expression in a concentration-dependent manner where 100 µM aminochrome increases GSTM2 expression by 2.1-fold (P < 0.001) at 3 h. The uptake of (3)H-aminochrome into U373MG cells was significantly reduced in the presence of...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-014-9500-1
更新日期:2015-04-01 00:00:00
abstract::The classical motor symptoms of Parkinson’s disease (PD) are preceded by non-motor symptoms in preclinical stages, including cognition impairment. The current drug treatment for PD is palliative and does not meet the clinical challenges of the disease, such as levodopa-induced dyskinesia, non-motor symptoms, and neuro...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-015-9566-4
更新日期:2016-01-01 00:00:00
abstract::Microglia are innate immune system cells which reside in the central nervous system (CNS). Resting microglia regulate the homeostasis of the CNS via phagocytic activity to clear pathogens and cell debris. Sometimes, however, to protect neurons and fight invading pathogens, resting microglia transform to an activated-f...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/s12640-019-00030-0
更新日期:2019-07-01 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::Integrin β8 is a key regulator of vascular homeostasis in brain development and in vitro studies show that β8 protects against oxygen-glucose deprivation-induced neuronal apoptosis. However, the role β8 plays in vivo in neonatal rats with hypoxic-ischemic (HI) brain injury is not known. Here, we report the function of...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-012-9312-0
更新日期:2012-11-01 00:00:00
abstract::In the slowly progressive neurodegenerative disorders like Parkinson's disease and Alzheimer's disease very different neuronal populations undergo degenerative processes, although the cascades of cellular events leading to death are supposed to be similar. We suggest that the complex pattern of degeneration in Parkins...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033793
更新日期:2000-01-01 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::Previous studies using monotypic nerve cell cultures have shown that bilirubin-induced neurological dysfunction (BIND) involves apoptosis and necrosis-like cell death, following neuritic atrophy and astrocyte activation,and that glycoursodeoxycholic acid (GUDCA) has therapeutic efficacy against BIND. Cross-talk betwee...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-013-9427-y
更新日期:2014-07-01 00:00:00
abstract::In humans, Down syndrome (DS) is caused by the presence of an extra copy of autosome 21. The most striking finding in DS patients is intellectual disability and the onset of Alzheimer's disease (AD)-like neuropathology in adulthood. Gene overdose is most likely to underlie both developmental impairments, as well as al...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-016-9613-9
更新日期:2016-07-01 00:00:00
abstract::Hyperphosphorylated tau is an important pathological agent in Alzheimer's disease (AD). Tau effluxes from the brain to the blood could potentially stimulate the production of naturally occurring antibodies (NAbs). We aimed to investigate whether NAbs to tau (NAbs-tau) was generated in human blood and to figure out the...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-020-00161-9
更新日期:2020-04-01 00:00:00
abstract::Alzheimer's disease (AD) is characterized by extracellular accumulation of β-amyloid peptides (Aβ) and intracellular neurofibrillary tangles, along with cognitive decline and neurodegeneration. The cognitive deficit is considered to be due to the dysfunction of hippocampal neurogenesis. Although L-3-n-butylphthalide (...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-018-9905-3
更新日期:2018-10-01 00:00:00
abstract::Parkinson's disease (PD) is a neurodegenerative disorder that is hallmarked by pathological changes associated with the death of dopaminergic neurons, particularly in the extrapyramidal system (substantia nigra pars compacta, striatum) of the brain. Although the causes of slow neuronal death in PD are unknown, both ge...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-015-9556-6
更新日期:2016-04-01 00:00:00
abstract::Mitochondria are the major site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, mitochondria produce most of the reactive oxygen species (ROS) in nucleated cells. Redox and bioenergetic abnormalities have been seen in mitochondria during the onset and progression of neurodegenerative diseases....
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00044-8
更新日期:2019-10-01 00:00:00
abstract::We present for discussion a possible molecular mechanism explaining the formation of reactive oxygen species involved in the neurodegenerative process of dopaminergic system in Parkinson's disease. This new hypothesis involves one-electron reduction of aminochrome to o-semiquinone radical, which seems to be the reacti...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033188
更新日期:2001-04-01 00:00:00
abstract::There has been a growing recognition of the role of neuroinflammation caused by microglia-exaggerated release of inflammatory mediators in the pathogenesis of Parkinson's disease (PD). Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous 38 amino acid containing neuropeptide that has been shown ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-014-9468-x
更新日期:2014-10-01 00:00:00
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...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-009-9028-y
更新日期:2009-04-01 00:00:00
abstract::Levetiracetam (LVT) is a relatively novel antiepileptic drug (AED) known to act through binding with the synaptic vesicular 2A (SV2A) protein, thus modulating the presynaptic neurotransmitter release. The tryptophan metabolite quinolinic acid (QUIN) acts as an excitotoxin when its brain concentrations reach toxic leve...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-017-9836-4
更新日期:2018-05-01 00:00:00
abstract::Aging plays a significant role in the progression of vascular diseases and vascular dysfunction. Activation of the ADP-ribosylation factor 6 and small GTPases by inflammatory signals may cause vascular permeability and endothelial leakage. Pro-inflammatory molecules have a significant effect on smooth muscle cells (SM...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/s12640-019-00047-5
更新日期:2019-10-01 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::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::Alzheimer disease (AD) is a major cause of dementia. Several mechanisms have been postulated to explain its pathogenesis, beta-amyloid (A beta toxicity, cholinergic dysfunction, Tau hyper-phosphorylation, oxidative damage, synaptic dysfunction and inflammation secondary to senile plaques, among others. Glial cells are...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033906
更新日期:2007-12-01 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