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 neuronal death. Despite great efforts, a potential causative agent leading to genetic mutation in HTT, manifesting the neurons more prone to oxidative stress, cellular inflammation, energy depletion and apoptotic death, has not been established yet. Current scenario concentrates on symptomatic pathologies to improvise the disease progression and to better the survival. Most of the therapeutic developments have been converged to rescue the protein homeostasis. In HD, abnormal expansion of glutamine repeats in the protein huntingtin leads to toxic aggregation of huntingtin which in turn impairs the quality control mechanism of cells through damaging the machineries involved in removal of aggregated abnormal protein. Therapeutic approaches to improve the efficiency of aggregate clearance through quality control mechanisms involve protein folding machineries such as chaperones and protein degradation machineries such as proteasome and autophagy. Also, to reduce protein aggregation by enhancing proper folding, to degrade and eliminate the aggregates are suggested to negatively regulate the HD progression associated with the disruption of protein homeostasis. This review focuses on the collection of therapeutic strategies targeting enhancement of protein quality control activity to delay the HD pathogenesis.
journal_name
Neurotox Resjournal_title
Neurotoxicity researchauthors
Rai SN,Singh BK,Rathore AS,Zahra W,Keswani C,Birla H,Singh SS,Dilnashin H,Singh SPdoi
10.1007/s12640-019-00087-xsubject
Has Abstractpub_date
2019-10-01 00:00:00pages
612-626issue
3eissn
1029-8428issn
1476-3524pii
10.1007/s12640-019-00087-xjournal_volume
36pub_type
杂志文章,评审abstract::Epigenetics, or alterations in the phenotype or gene expression due to mechanisms other than changes in the underlying DNA sequence, reflects the sensitivity and responsiveness of human and animal brains in constantly varying circumstances regulating gene expression profiles that define the biomarkers and present the ...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/s12640-010-9163-5
更新日期:2010-11-01 00:00:00
abstract::Reward-related incentive learning involves the acquisition by neutral stimuli of an enhanced ability to elicit approach and other responses. Previous studies have shown that both dopamine (DA) and glutamate (Glu) play critical roles in this type of learning. Signaling molecules are intracellular messengers that partic...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033301
更新日期:2004-01-01 00:00:00
abstract::One of the authors has incorrect family name spelling in the original article. Michael Ashner should read as Michael Aschner. ...
journal_title:Neurotoxicity research
pub_type: 杂志文章,已发布勘误
doi:10.1007/s12640-019-00153-4
更新日期:2020-03-01 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::The complexity of the genome is regulated by epigenetic mechanisms, which act on the level of DNA, histones, and nucleosomes. Epigenetic machinery is involved in various biological processes, including embryonic development, cell differentiation, neurogenesis, and adult cell renewal. In the last few years, it has beco...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/s12640-014-9508-6
更新日期:2015-02-01 00:00:00
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::Maternal hyperhomocysteinemia is one of the common complications of pregnancy that causes offspring cognitive deficits during postnatal development. In the present work, we evaluated the effect of prenatal hyperhomocysteinemia on structural and ultrastructural organization, neuronal and glial cell number, apoptosis (c...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-020-00233-w
更新日期:2020-08-01 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::MDMA (3,4-methylenedioxymethamphetamine) is a psychostimulant popular as a recreational drug because of its effect on mood and social interactions. MDMA acts at dopamine (DA) transporter (DAT) and serotonin (5-HT) transporter (SERT) and is known to induce damage of dopamine and serotonin neurons. MDMA is often ingeste...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-017-9831-9
更新日期:2018-04-01 00:00:00
abstract::Thioredoxin (Trx) and glyoxalase (Glo) systems have been suggested to be molecular targets of methylglyoxal (MGO). This highly reactive endogenous compound has been associated with the development of neurodegenerative pathologies and cell death. In the present study, the glutathione (GSH), Trx, and Glo systems were in...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-017-9738-5
更新日期:2017-10-01 00:00:00
abstract::This study was aimed to investigate neuropathological changes in adult and aged rats subjected to supplementary iron administration in a critical postnatal period to study the contribution of environmental risk factors to the pathogenesis of neurodegenerative disorders. Ten rats received a single daily oral administra...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-010-9235-6
更新日期:2011-08-01 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::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::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::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::Cellular oxidative stress and energy failure were shown to be involved in Glutamate (L-Glu) neurotoxicity, whereas, acetyl-L-carnitine (ALCAR) and ±DL-α-lipoic acid (LA) are known to be key players in the mitochondrial energy production. To evaluate the effects of the above antioxidants, adult rats were pretreated wit...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-010-9165-3
更新日期:2011-02-01 00:00:00
abstract::Myelin abnormalities, oligodendrocyte damage, and concomitant glia activation are common characteristics of demyelinating diseases of the central nervous system. Administration of the neurotoxicant cuprizone (CPZ) has been extensively used to establish a reproducible mouse model of demyelination. However, its effects ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00154-3
更新日期:2020-03-01 00:00:00
abstract::The isolated sciatic nerve of the frog was used to assess the effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) on the peripheral nervous system. For each experiment, both sciatic nerves were used. The evoked compound action potentials of the nerves were monitored for over 48 h as an indication of their ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1080/10298420290007592
更新日期:2002-02-01 00:00:00
abstract::Multiple lines of evidence demonstrate that reactive oxygen species (ROS) are involved in regulation of normal cell metabolism as second messengers. Under extreme conditions, these molecules induce oxidative stress, which may stimulate (or accompany) a number of neurodegenerative processes. In the glutamatergic system...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033454
更新日期:2004-01-01 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 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::Parkinson's disease (PD) represents one of the neurodegenerative disorders which are caused by degeneration of dopaminergic neurons in the nigrostriatal pathway. Different toxins, e.g., 6-hydroxydopamine (6-OHDA), are used to model PD in animals. 6-OHDA is a neurotoxin which damages catecholaminergic neurons via produ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-017-9824-8
更新日期:2018-04-01 00:00:00
abstract::2-Hydroxypropyl-β-cyclodextrin (HPβCD), a cholesterol chelator, is being used to treat diseases associated with abnormal cholesterol metabolism such as Niemann-Pick C1 (NPC1). However, the high doses of HPβCD needed to slow disease progression may cause hearing loss. Previous studies in mice have suggested that HPβCD ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-020-00252-7
更新日期:2020-10-01 00:00:00
abstract::Parkinson's disease is a slowly progressing disease, due to a lesion of dopaminergic neurons in the substantia nigra and a dramatic loss of dopamine in the striatum. It is now accepted that several environmental agents including the herbicide paraquat (PQ) may contribute to its pathogenesis. However, till now nothing ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-010-9153-7
更新日期:2011-01-01 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::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::Early-life stress is a potent risk factor for development of psychiatric conditions such as depression. The underlying mechanisms remain poorly understood. Here, we used the early-life social isolation (ESI) model of early-life stress in rats to characterize development of depressive-like behavior, the role of microgl...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-016-9696-3
更新日期:2017-05-01 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::The aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-013-9403-6
更新日期:2013-10-01 00:00:00
abstract::GSK3beta is prominent for its role in apoptosis signaling and has been shown to be involved in Parkinson's disease (PD) pathogenesis. The overall effects of GSK3beta activity on cell fate are well-established, but the effects of mitochondrial GSK3beta activity on mitochondrial function and cell fate are unknown. Here ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033861
更新日期:2008-12-01 00:00:00