Abstract:
:Specific variations in the amino acid sequence of prion protein (PrP) are key determinants of susceptibility to prion diseases. We previously showed that an amino acid substitution specific to canids confers resistance to prion diseases when expressed in mice and demonstrated its dominant-negative protective effect against a variety of infectious prion strains of different origins and characteristics. Here, we show that expression of this single amino acid change significantly increases survival time in transgenic mice expressing bank vole cellular prion protein (PrPC), which is inherently prone to misfolding, following inoculation with two distinct prion strains (the CWD-vole strain and an atypical strain of spontaneous origin). This amino acid substitution hinders the propagation of both prion strains, even when expressed in the context of a PrPC uniquely susceptible to a wide range of prion isolates. Non-inoculated mice expressing this substitution experience spontaneous prion formation, but showing an increase in survival time comparable to that observed in mutant mice inoculated with the atypical strain. Our results underscore the importance of this PrP variant in the search for molecules with therapeutic potential against prion diseases.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Otero A,Hedman C,Fernández-Borges N,Eraña H,Marín B,Monzón M,Sánchez-Martín MA,Nonno R,Badiola JJ,Bolea R,Castilla Jdoi
10.1007/s12035-019-1535-0subject
Has Abstractpub_date
2019-09-01 00:00:00pages
6501-6511issue
9eissn
0893-7648issn
1559-1182pii
10.1007/s12035-019-1535-0journal_volume
56pub_type
杂志文章abstract::Neuroblastoma (NB) is an extracranial solid cancer and the most common cancer in infancy. Despite the standard treatment for NB is based on the combination of chemotherapeutic drugs such as doxorubicin, vincristine, cyclophosphamide, and cisplatin, chemoresistance occurs over the time. The aim of the present research ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0575-6
更新日期:2018-04-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease characterized by degeneration of upper and lower motor neurons (MNs), generalized weakness and muscle atrophy. The "neurocentric" view of ALS assumes that the disease primarily affects motor neurons, while muscle alterations only...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-013-8578-4
更新日期:2014-04-01 00:00:00
abstract::Adult neural progenitor cells (NPCs) induce post-ischemic long-term neuroprotection and brain remodeling by releasing of survival- and plasticity-promoting mediators. To evaluate whether secreted factors may mimic neuroprotective and restorative effects of NPCs, we exposed male C57BL6 mice to focal cerebral ischemia a...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9748-y
更新日期:2017-03-01 00:00:00
abstract::Linoleic acid (LA, 18:2n-6) is a precursor to arachidonic acid (AA, 20:4n-6), which can be converted by brain lipoxygenase and cyclooxygenase (COX) enzymes into various lipid mediators involved in the regulation of brain immunity. Brain AA metabolism is activated in rodents by the bacterial endotoxin, lipopolysacchari...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9968-1
更新日期:2017-08-01 00:00:00
abstract::Extracellular nucleotides, particularly adenosine 5'-triphosphate (ATP), act as signaling molecules in the inner ear. Roles as neurotransmitters, neuromodulators, and as autocrine or paracrine humoral factors are evident. The diversity of the signaling pathways for nucleotides, which include a variety of ATP-gated ion...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02740601
更新日期:1998-02-01 00:00:00
abstract::Axonal damage is a major factor contributing to disease progression in multiple sclerosis (MS) patients. On the histological level, acute axonal injury is most frequently analyzed by anti-amyloid precursor protein immunohistochemistry. To what extent this method truly detects axonal injury, and whether other proteins ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1353-9
更新日期:2019-06-01 00:00:00
abstract::Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem of vertebrates. Glycine is accumulated into synaptic vesicles by a proton-coupled transport system and released to the synaptic cleft after depolarization of the presynaptic terminal. The inhibitory action of glycine is mediated by pentame...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02740653
更新日期:1997-06-01 00:00:00
abstract::The Shadoo protein (Sho) exhibits homology to the hydrophobic region of the cellular isoform of prion protein (PrPC). As prion-infected brains gradually accumulate infectivity-associated isoforms of prion protein (PrPSc), levels of mature endogenous Sho become reduced. To study the regulatory effect of the proteostati...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-019-1623-1
更新日期:2019-11-01 00:00:00
abstract::Genetic disruptions of spindle/centrosome-associated WD40-repeat protein 62 (WDR62) are causative for autosomal recessive primary microcephaly (MCPH) and a broader range of cortical malformations. Since the identification of WDR62 as encoded by the MCPH2 locus in 2010, recent studies that have deleted/depleted WDR62 i...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-017-0778-x
更新日期:2018-07-01 00:00:00
abstract::Parkinson's disease (PD) is a highly prevalent neurodegenerative disease for which no disease-modifying treatments are available, mainly because knowledge about its pathogenic mechanism is still incomplete. Recently, a key role for lipids emerged, but lipid profiling of brain samples from human subjects is demanding. ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-019-01733-3
更新日期:2020-02-01 00:00:00
abstract::Addiction is a chronic psychiatric disease which represents a global problem, and stress can increase drug addiction and relapse. Taking into account frequent concomitance of nicotine dependence and stress, the purpose of the present study was to assess behavioral and biochemical effects of chronic unpredictable mild ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0585-4
更新日期:2018-04-01 00:00:00
abstract::Paclitaxel is a chemotherapeutic agent used to treat solid tumours. However, it causes an acute and neuropathic pain syndrome that limits its use. Among the mechanisms involved in neuropathic pain caused by paclitaxel is activation of kinin receptors. Angiotensin converting enzyme (ACE) inhibitors can enhance kinin re...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0275-7
更新日期:2017-12-01 00:00:00
abstract::Military personnel are often subjected to sleep deprivation (SD) during combat operations. Since SD is a severe stress and alters neurochemical metabolism in the brain, a possibility exists that acute or long-term SD will influence blood-brain barrier (BBB) function and brain pathology. This hypothesis was examined in...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9236-9
更新日期:2015-10-01 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::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::Early life stress is considered a risk factor for the development of long-term psychiatric disorders. Maternal deprivation (MD) is a useful paradigm to understand the neurobiological underpinnings of early stress-induced changes in neurodevelopment trajectory. The goal of the present study was to examine the effects o...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02164-1
更新日期:2020-10-15 00:00:00
abstract::Copper is an essential nutrient that plays a fundamental role in the biochemistry of the central nervous system, as evidenced by patients with Menkes disease, a fatal neurodegenerative disorder of childhood resulting from the loss-of-function of a copper-transporting P-type adenosine triphosphatase (ATPase). Despite c...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1385/MN:33:2:81
更新日期:2006-04-01 00:00:00
abstract::Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with unknown etiology. Recent experimental evidences suggest the contribution of non-coding RNAs (ncRNAs) in the pathophysiology of ASD. In this work, we aimed to investigate the expression profile of the ncRNA class of circular RNAs (circR...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-01878-6
更新日期:2020-05-01 00:00:00
abstract::(-)-Epigallocatechin-3‑gallate (EGCG), the predominant constituent of green tea, has been demonstrated to be neuroprotective against acute ischemic stroke. However, the long-term actions of EGCG on neurogenesis and functional recovery after ischemic stroke have not been identified. In this study, C57BL/6 mice underwen...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9924-0
更新日期:2017-07-01 00:00:00
abstract::There is variety of stem cell sources but problems in ethical issues, contamination, and normal karyotype cause many limitations in obtaining and using these cells. The cells in Wharton's jelly region of umbilical cord are abundant and available stem cells with low immunological incompatibility, which could be conside...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0090-1
更新日期:2017-09-01 00:00:00
abstract::Beginning in the early stages of Alzheimer's disease (AD), the hippocampus reduces its functional connections to other cortical regions due to synaptic depletion. However, little is known regarding connectivity abnormalities within the hippocampus. Here, we describe rostral-caudal hippocampal convergence (rcHC), a met...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-019-01671-0
更新日期:2019-12-01 00:00:00
abstract::The aim of this work was to study the effect of glucagon-like peptide-2 (GLP-2) on the cyclic guanosine monophosphate (cGMP) signalling pathway and whether insulin or epidermal growth factor (EGF) might modulate the effects of GLP-2. GLP-2 produced a dose-dependent decrease in intracellular sodium nitroprusside-induce...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-012-8298-1
更新日期:2012-10-01 00:00:00
abstract::Cytosolic phospholipase A2 (cPLA2) mediates oligomeric amyloid-β peptide (oAβ)-induced oxidative and inflammatory responses in glial cells. Increased activity of cPLA2 has been implicated in the neuropathology of Alzheimer's disease (AD), suggesting that cPLA2 regulation of oAβ-induced microglial activation may play a...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1304-5
更新日期:2019-05-01 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::P2C-type ATPases are a subfamily of P-type ATPases comprising Na(+)/K(+)-ATPase and H(+)/K(+)-ATPase. Na(+)/K(+)-ATPase is ubiquitously expressed and has been implicated in several neurological diseases, whereas H(+)/K(+)-ATPase is found principally in the colon, stomach, and kidney. Both ATPases have two subunits, α ...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-014-9076-z
更新日期:2016-03-01 00:00:00
abstract::Autism and epilepsy are diseases which have complex genetic inheritance. Genome-wide association and other genetic studies have implicated at least 500+ genes associated with the occurrence of autism spectrum disorders (ASD) including the human semaphorin 3F (Sema 3F) and neuropilin 2 (NRP2) genes. However, the geneti...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1450-9
更新日期:2019-08-01 00:00:00
abstract::Repetitive transcranial magnetic stimulation (rTMS) is a novel physiological therapy that has been adopted to clinically treat psychiatric disorders. Our previous study indicated the potential therapeutic effect of rTMS on posttraumatic stress disorder (PTSD). However, the exact molecular mechanism is elusive. Current...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0602-7
更新日期:2018-05-01 00:00:00
abstract::Alzheimer's disease (AD) is characterized by intracellular and extracellular protein aggregates, including microtubule-associated protein tau and cleavage product of amyloid precursor protein, β-amyloid (Aβ). Tissue transglutaminase (tTG) is a calcium-dependent enzyme that cross-links proteins forming a γ-glutamyl-ε-l...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9413-x
更新日期:2016-10-01 00:00:00
abstract::Different factors may contribute to the development of neurodegenerative diseases. Among them, metabolic syndrome (MS), which has reached epidemic proportions, has emerged as a potential element that may be involved in neurodegeneration. Furthermore, studies have shown the importance of the sirtuin family in neuronal ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9927-x
更新日期:2017-07-01 00:00:00
abstract::Multiple sclerosis (MS) is an autoimmune, inflammatory disease of the central nervous system (CNS). We have measured the levels of over 20 non-esterified sterols in plasma and cerebrospinal fluid (CSF) from patients suffering from MS, inflammatory CNS disease, neurodegenerative disease and control patients. Analysis w...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0281-9
更新日期:2017-12-01 00:00:00