Abstract:
:Oxidative stress-induced damage is a major mechanism in the pathophysiology of amyotrophic lateral sclerosis (ALS). A recent human clinical trial showed that the combination of nicotinamide riboside (NR) and pterostilbene (PT), molecules with potential to interfere in that mechanism, was efficacious in ALS patients. We examined the effect of these molecules in SOD1G93A transgenic mice, a well-stablished model of ALS. Assessment of neuromotor activity and coordination was correlated with histopathology, and measurement of proinflammatory cytokines in the cerebrospinal fluid. Cell death, Nrf2- and redox-dependent enzymes and metabolites, and sirtuin activities were studied in isolated motor neurons. NR and PT increased survival and ameliorated ALS-associated loss of neuromotor functions in SOD1G93A transgenic mice. NR and PT also decreased the microgliosis and astrogliosis associated with ALS progression. Increased levels of proinflammatory cytokines were observed in the cerebrospinal fluid of mice and humans with ALS. NR and PT ameliorated TNFα-induced oxidative stress and motor neuron death in vitro. Our results support the involvement of oxidative stress, specific Nrf2-dependent antioxidant defenses, and sirtuins in the pathophysiology of ALS. NR and PT interfere with the mechanisms leading to the release of proapoptotic molecular signals by mitochondria, and also promote mitophagy.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Obrador E,Salvador R,Marchio P,López-Blanch R,Jihad-Jebbar A,Rivera P,Vallés SL,Banacloche S,Alcácer J,Colomer N,Coronado JA,Alandes S,Drehmer E,Benlloch M,Estrela JMdoi
10.1007/s12035-020-02188-7subject
Has Abstractpub_date
2020-11-10 00:00:00eissn
0893-7648issn
1559-1182pii
10.1007/s12035-020-02188-7pub_type
杂志文章abstract::Phospholipase C beta 1 (PLCβ1) expresses in gliomas and cultured glial cells, but its expression is barely detectable in normal glial cells. We analyzed data from Gene Expression Omnibus (GEO-GDSxxx), The Cancer Genome Atlas (TCGA), and the Repository for Molecular Brain Neoplasia Data (REMBRANDT) to explore the poten...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9518-2
更新日期:2016-11-01 00:00:00
abstract::Recent studies show that myostatin mRNA expression is found in some regions of the brain. However, the functional significance of this is currently unknown. We therefore investigated myostatin expression and function in the brain. In this study, we used immunohistochemistry, in situ hybridization, and RT-PCR analysis ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-012-8342-1
更新日期:2013-02-01 00:00:00
abstract::YKL-40 is the most highly expressed gene in glioblastoma compared with normal brain tissues. Previous studies assessing the association between YKL-40 and survival in glioblastoma patients reported varying magnitude of estimates. The objective of this meta-analysis was to determine the prognostic value of YKL-40 in gl...
journal_title:Molecular neurobiology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s12035-016-9878-2
更新日期:2017-07-01 00:00:00
abstract::While prion diseases have been described in numerous species, some, including those of the Canidae family, appear to show resistance or reduced susceptibility. A better understanding of the factors underlying prion susceptibility is crucial for the development of effective treatment and control measures. We recently d...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0832-8
更新日期:2018-07-01 00:00:00
abstract::α-Synuclein (α-syn) has been recognized to induce neuroinflammation and to disturb nerve repair process in Parkinson's disease. However, the potential mechanisms underlying α-syn-induced impairment of adult neurogenesis remain unclear. In the present study, A53T mutant α--synuclein transgenic (A53Ttg/tg) mice, caspase...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9620-5
更新日期:2016-12-01 00:00:00
abstract::Alzheimer's disease (AD) is the most prevalent type of dementia in elderly people. There are decreased melatonin levels in the serum of AD patients, and melatonin supplements are able to reverse AD pathology and memory deficits in many animal experiments and clinical trials. However, the underlying mechanism regarding...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-012-8355-9
更新日期:2013-02-01 00:00:00
abstract::Statins have proven their effectiveness in the treatment of cardiovascular disease. This class of drugs has also attracted attention as a potential treatment for dissimilar diseases such as certain types of cancers and neurodegenerative diseases. What appears to be a contradiction is that, in the case of cancer, it ha...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-013-8496-5
更新日期:2013-10-01 00:00:00
abstract::The role of matrix metalloproteinase-12 (MMP-12) in the pathogenesis of several inflammatory diseases such as chronic obstructive pulmonary disease, emphysema, and asthma is well established. Several new studies and recent reports from our laboratory and others highlighted the detrimental role of MMP-12 in the pathoge...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-017-0418-5
更新日期:2018-02-01 00:00:00
abstract::The study of sporadic Alzheimer's disease etiology, now more than ever, needs an infusion of new concepts. Despite ongoing interest in Alzheimer's disease, the basis of this entity is not yet clear. At present, the best-established and accepted "culprit" in Alzheimer's disease pathology by most scientists is the amylo...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-013-8439-1
更新日期:2013-12-01 00:00:00
abstract::Three early signals of asymmetry have been described to occur in a single neurite of neurons at stage 2 of differentiation (before polarization) and shown to be essential for neuronal polarization: (i) accumulation of stable microtubules, (ii) enrichment of the plasma membrane with activatable IGF-1r, and (iii) polari...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0144-4
更新日期:2017-10-01 00:00:00
abstract::Ketamine is used as a general anesthetic, and recent data suggest that anesthetics can cause neuronal damage when exposure occurs during development. The precise mechanisms are not completely understood. To evaluate the degree of ketamine-induced neuronal toxicity, neural stem cells were isolated from gestational day ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9248-5
更新日期:2015-10-01 00:00:00
abstract::The development of in vitro amplification systems allows detecting femtomolar amounts of prion protein scrapie (PrP(Sc)) in human cerebrospinal fluid (CSF). We performed a CSF study to determine the effects of prion disease type, codon 129 genotype, PrP(Sc) type, and other disease-related factors on the real-time quak...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-014-8709-6
更新日期:2015-02-01 00:00:00
abstract::In human glioma tumours, heme oxygenase-1 (HO-1) is overexpressed when compared with normal brain tissues and during oligodendroglioma progression. However, the molecular mechanisms mediated by HO-1 to promote glioblastoma remain unknown. We therefore aimed at investigating the effect of HO-1 expression and its select...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-01869-7
更新日期:2020-05-01 00:00:00
abstract::Alzheimer's disease (AD) is one of the most common forms of dementia among elder people, which is a progressive neurodegenerative disease that results from a chronic loss of cognitive activities. It has been observed that AD is multifactorial, hence diverse pharmacological targets that could be followed for the treatm...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-020-02116-9
更新日期:2021-01-01 00:00:00
abstract::Angelman syndrome (AS) is a neurodevelopmental disorder largely caused by the loss of function of maternally inherited UBE3A. UBE3A-maternal deficient mice (AS mice) exhibit many typical features of AS including cognitive and motor deficits but the underlying mechanism of these behavioral abnormalities is poorly under...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0080-3
更新日期:2017-09-01 00:00:00
abstract::Neuronal plasticity can be defined as adaptive changes in structure and function of the nervous system, an obvious example of which is the capacity to remember and learn. Long-term potentiation and long-term depression are the experimental models of memory in the central nervous system (CNS), and have been frequently ...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02802028
更新日期:1998-01-01 00:00:00
abstract::Alzheimer's disease (AD), a neurodegenerative disorder exhibiting a gradual decline in cognitive function, is characterized by the presence of neuritic plaques composed of neurofibrillary tangles and amyloid-β (Aβ) peptide. Available drugs for AD therapy have small effect sizes and do not alter disease progression. Se...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-013-8401-2
更新日期:2013-06-01 00:00:00
abstract::Once infected by HIV-1, microglia abundantly produce accessory protein Nef that enhances virus production and infectivity, but little is known about its intracellular compartmentalization, trafficking mode(s), and release from microglia. Here, we transfected immortalized human microglia with a plasmid encoding Nef tag...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1072-2
更新日期:2019-01-01 00:00:00
abstract::Dendritic spines, a special kind of structure in nerve cells, play a key role in performing cellular function. Structural abnormalities of the dendritic spine may contribute to synaptic dysfunction and have been implicated in memory formation. However, the molecular mechanisms that trigger dendritic spine loss remain ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0349-6
更新日期:2018-01-01 00:00:00
abstract::The administration of the anorexigenic drug d,l-fenfluramine (Ponderax) to laboratory animals results in a dose-dependent reduction in presynaptically located serotonergic reuptake transporter protein. This long-term effect may represent an altered mechanism of synthesis of the transporter (downregulation). Alternativ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/BF02740693
更新日期:1995-08-01 00:00:00
abstract::Alpha synuclein (α-synuclein) is a neuronal protein found predominately in presynaptic terminals. While the pathological effect of α-synuclein aggregates has been a topic of intense study in several neurodegenerative conditions, less attention has been placed on changes in monomeric α-synuclein and related physiologic...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02123-w
更新日期:2021-01-01 00:00:00
abstract::Alzheimer's disease (AD) is the most prevalent form of dementia in the world. The neuropathological characteristics of AD patients are the accumulation of extracellular plaques of β-amyloid (Aβ) and intracellular hyperphosphorylated tau protein. Transthyretin (TTR) may alleviate AD symptom by reducing Aβ concentration...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0065-2
更新日期:2017-09-01 00:00:00
abstract::Maternal separation (MS) causes long-lasting epigenetic changes in the brain and increases vulnerability to traumatic events in adulthood. Of interest, there may be sex-specific differences in these epigenetic changes. In this study, the extent of histone acetylation in the hippocampus (HIP) and the expression of BDNF...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02224-6
更新日期:2020-11-27 00:00:00
abstract::Metabolic defects are common pathological phenomena following traumatic brain injury (TBI) which contribute to poor prognosis. Brain-derived neurotrophic factor (BDNF) is an important regulator of neuronal survival, development, function, and plasticity. This study was designed to investigate the potential effects of ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0576-5
更新日期:2018-04-01 00:00:00
abstract::Microglial activation is a pathological feature of many neurodegenerative diseases and the role of cellular lipids in these diseases is mostly unknown. It was known that the special ether lipid plasmalogens (Pls) were reduced in the brain and blood samples of Alzheimer's disease (AD) patients. It has recently been rep...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1307-2
更新日期:2019-05-01 00:00:00
abstract::Neonatal hypoxia-ischemia (HI) is among the main causes of mortality and morbidity in newborns. Experimental studies show that the immature rat brain is less susceptible to HI injury, suggesting that changes that occur during the first days of life drastically alter its susceptibility. Among the main developmental cha...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02261-1
更新日期:2021-01-08 00:00:00
abstract::Hippocampus-dependent memories, such as social recognition (SRM), are modulated by neurogenesis. However, the precise role of newborn neurons in social memory processing is still unknown. We showed previously that 1 week of enriched environment (EE) is sufficient to increase neurogenesis in the hippocampus (HIP) and t...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9922-2
更新日期:2017-07-01 00:00:00
abstract::In neurons, the convergence of multiple intracellular signaling cascades leading to cAMP-responsive element-binding protein (CREB) activation suggests that this transcription factor plays a critical role in integrating different inputs and mediating appropriate neuronal responses. The nature of this transcriptional re...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-011-8209-x
更新日期:2011-12-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common cause of dementia among elderly people. Despite enormous efforts, the pathogenesis of AD still remains unclear and no drug has yet been proved to be disease-modifying. As the basis of learning and memory, the plasticity of synapse and dendritic spine has been impaired during...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02183-y
更新日期:2020-11-03 00:00:00
abstract::NMDA receptor signaling is critical for the development of synaptic plasticity, learning, and memory, and dysregulation of NMDAR signaling is implicated in a number of neurological disorders including schizophrenia (SZ). Previous work has demonstrated that the STriatal-Enriched protein tyrosine Phosphatase 61 kDa (STE...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0555-x
更新日期:2018-04-01 00:00:00