Abstract:
:Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease that disrupts the normally reliable neurotransmission at the neuromuscular junction (NMJ). This disruption is thought to result from an autoantibody-mediated removal of a subset of the P/Q-type Ca(2+) channels involved with neurotransmitter release. With less neurotransmitter release at the NMJ, LEMS patients experience debilitating muscle weakness. The underlying cause of LEMS in slightly more than half of all patients is small cell lung cancer, and cancer therapy is the priority for these patients. In the remaining cases, the cause of LEMS is unknown, and these patients often rely on symptomatic treatment options, as there is no cure. However, current symptomatic treatment options, such as 3,4-diaminopyridine (3,4-DAP), can have significant dose-limiting side effects; thus, additional treatment approaches would benefit LEMS patients. Recent studies introduced a novel Ca(2+) channel agonist (GV-58) as a potential therapeutic alternative for LEMS. Additionally, this work has shown that GV-58 and 3,4-DAP interact in a supra-additive manner to completely restore the magnitude of neurotransmitter release at the NMJs of a LEMS mouse model. In this review, we discuss synaptic mechanisms for reliability at the NMJ and how these mechanisms are disrupted in LEMS. We then discuss the current treatment options for LEMS patients, while also considering recent work demonstrating the therapeutic potential of GV-58 alone and in combination with 3,4-DAP.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Tarr TB,Wipf P,Meriney SDdoi
10.1007/s12035-014-8887-2subject
Has Abstractpub_date
2015-08-01 00:00:00pages
456-63issue
1eissn
0893-7648issn
1559-1182pii
10.1007/s12035-014-8887-2journal_volume
52pub_type
杂志文章,评审abstract::The human KCTD13 gene is located within the 16p11.2 locus and copy number variants of this locus are associated with a high risk for neuropsychiatric diseases including autism spectrum disorder and schizophrenia. Studies in zebrafish point to a role of KCTD13 in proliferation of neural precursor cells which may contri...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-019-01727-1
更新日期:2020-02-01 00:00:00
abstract::Social isolation during the vulnerable period of adolescence produces emotional dysregulation that often manifests as abnormal behavior in adulthood. The enduring consequence of isolation might be caused by a weakened ability to forget unpleasant memories. However, it remains unclear whether isolation affects unpleasa...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-014-8917-0
更新日期:2015-12-01 00:00:00
abstract::Inflammation plays a crucial role in the pathogenesis of stroke. This study aims to determine lipoprotein (a) [Lp(a)] levels in serum and to investigate their associations with stroke recurrence events in a 3-month follow-up study in patients with acute ischemic stroke (AIS). Serum Lp(a) levels were determined in 203 ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0346-9
更新日期:2018-01-01 00:00:00
abstract::Stroke is considered as the second leading cause of death worldwide. The survivors of stroke experience different levels of impairment in brain function resulting in debilitating disabilities. Current therapies for stroke are primarily palliative and may be effective in only a small population of stroke patients. In t...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9740-6
更新日期:2017-03-01 00:00:00
abstract::Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a severe deficiency in the activity of the branched-chain α-keto acid dehydrogenase complex, leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine. Infections have a significant role in precipitating ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-013-8618-0
更新日期:2014-10-01 00:00:00
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 ag...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-019-1535-0
更新日期:2019-09-01 00:00:00
abstract::Previous studies have provided evidence for axon-to-myelin transfer of intact lipids and lipid precursors for reutilization by myelin enzymes. Several of the lipid constituents of myelin showed significant contralateral/ipsilateral ratios of incorporated radioactivity, indicative of axonal origin, whereas proteins and...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02780551
更新日期:1992-07-01 00:00:00
abstract::Up to now, survivin has been recommended as a prognostic and diagnostic indicator in glioma patients. However, there are still many controversies. Here, a meta-analysis was conducted to draw a more definitive conclusion on the correlation of survivin with overall survival (OS), age, gender, and WHO grade. Eligible stu...
journal_title:Molecular neurobiology
pub_type: 杂志文章,meta分析,收录出版
doi:10.1007/s12035-014-8823-5
更新日期:2015-01-01 00:00:00
abstract::Vimentin is an intermediate filament (also known as nanofilament) protein expressed in several cell types of the central nervous system, including astrocytes and neural stem/progenitor cells. Mutation of the vimentin serine sites that are phosphorylated during mitosis (VIM SA/SA ) leads to cytokinetic failures in fibr...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0759-0
更新日期:2018-07-01 00:00:00
abstract::Mild cognitive impairment (MCI) is considered as an intermediate zone between normal aging and dementia. The most prominent feature of MCI is an isolated mild decline in memory, whereas other cognitive functions remain intact. The symptoms of vascular cognitive impairment (VCI) range from MCI to dementia, and an anima...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9610-7
更新日期:2016-12-01 00:00:00
abstract::Type 2 diabetes (T2D) is a modern socioeconomic burden, mostly due to its long-term complications affecting nearly all tissues. One of them is the brain, whose dysfunctional intracellular quality control mechanisms (namely autophagy) may upregulate apoptosis, leading to cognitive dysfunction and Alzheimer disease (AD)...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0622-3
更新日期:2018-05-01 00:00:00
abstract::CX3CL1 (fractalkine) is the only member of the CX3C (delta) subfamily of chemokines which is unique and combines the properties of both chemoattractant and adhesion molecules. The two-form ligand can exist either in a soluble form, like all other chemokines, and as a membrane-anchored molecule. CX3CL1 discloses its bi...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-016-9787-4
更新日期:2017-04-01 00:00:00
abstract::Exposure to general anesthesia (GA) during critical stages of brain development induces widespread neuronal apoptosis and causes long-lasting behavioral deficits in numerous animal species. Although several studies have focused on the morphological fate of neurons dying acutely by GA-induced developmental neuroapoptos...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9246-7
更新日期:2015-10-01 00:00:00
abstract::Inhalational general anesthetics, such as sevoflurane and isoflurane, modulate a subset of brain Kv1 potassium channels. However, the Kv1.2 channel is resistant to propofol, a commonly used intravenous alkylphenol anesthetic. We hypothesize that propofol binds to a presumed pocket involving the channel's S4-S5 linker,...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0437-2
更新日期:2018-02-01 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
abstract::A disintegrin and metalloproteinase 10 (ADAM10) is a synaptic enzyme that has been previously shown to limit amyloid-β1-42 (Aβ1-42) peptide formation in Alzheimer's disease (AD). Furthermore, ADAM10 participates to spine shaping through the cleavage of adhesion molecules and its activity is under the control of synapt...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-019-1583-5
更新日期:2019-10-01 00:00:00
abstract::Disturbance of neuregulin-1β/ErbB4 signaling is considered to be associated with brain ischemia, but the mechanisms of this disruption are largely unknown. In the present study, we provide evidence that degradation of ErbB4 is involved in neuronal cell death in response to ischemia. Our data showed that the applicatio...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9275-2
更新日期:2016-05-01 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::Tissues within the central nervous system (CNS) have generally been regarded as immunologically privileged. However, in recent decades, it has been shown that immune reactions in the CNS continuously occur via various types of inflammation following autoimmune diseases and mechanical insults such as spinal cord injury...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-013-8398-6
更新日期:2013-06-01 00:00:00
abstract::Huntington's disease (HD) is a devastating neurodegenerative disease caused by cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin gene. Growing evidence supports the regulatory functions of long noncoding RNAs (lncRNAs) in the disease process, but little is known about the association between ln...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9928-9
更新日期:2017-03-01 00:00:00
abstract::Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus. The aim of this meta-analysis was to evaluate the effects of methylenetetrahydrofolate reductase (MTHFR) 677 C>T and ACE I/D polymorphisms in the development of DPN. We systematically reviewed published studies on MTHFR 677 C>T ...
journal_title:Molecular neurobiology
pub_type: 杂志文章,meta分析
doi:10.1007/s12035-016-9823-4
更新日期:2017-05-01 00:00:00
abstract::Lysine-specific demethylase 1 (LSD1/KDM1A) plays an important role in complex cellular processes such as differentiation, proliferation, apoptosis, and cell cycle progression. It has recently been demonstrated that during development, downregulation of LSD1 inhibits cell proliferation, modulates the expression of cell...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9206-2
更新日期:2016-05-01 00:00:00
abstract::A growing body of evidence indicates that pathological forms of amyloid beta (Aβ) peptide contribute to neuronal degeneration and synaptic loss in Alzheimer's disease (AD). In this study, we investigated the impact of exogenous Aβ1-42 oligomers (AβO) and endogenously liberated Aβ peptides on transcription of genes for...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-019-01819-y
更新日期:2020-03-01 00:00:00
abstract::The induction of synthesis or release of endogenous neurotrophic factors in the brain by low-molecular-weight drugs could be a feasible alternative for the direct administration of neurotrophic factors for the treatment of central nervous system disorders. Recent data suggest that several drugs already in clinical use...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1385/MN:29:3:289
更新日期:2004-06-01 00:00:00
abstract::Epigenetic and regulatory elements provide an additional layer of complexity to the heterogeneity of anxiety disorders. MicroRNAs (miRNAs) are a class of small, noncoding RNAs that have recently drawn interest as epigenetic modulators of gene expression in psychiatric disorders. miRNAs elicit their effects by binding ...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-012-8374-6
更新日期:2013-04-01 00:00:00
abstract::Glial cell line-derived neurotrophic factor (GDNF), which belongs to transforming growth factor β superfamily, plays important roles in glioma pathogenesis. Gdnf mRNA is aberrantly increased in glioma cells, but the underlying transcription mechanism is unclear. Here, we found that although the base sequence in the pr...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-013-8443-5
更新日期:2013-12-01 00:00:00
abstract::This review describes the modulation of the GABAa receptor by steroid hormones and barbiturates and proposes guidelines for further research. Having examined the complex organization of the GABAa receptor complex and the multiple allosteric interactions between its drug and transmitter/modulator binding sites, the pos...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02740608
更新日期:1989-01-01 00:00:00
abstract::Accumulating evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play important roles in several neurodegenerative disorders. Therefore, development of methods for microglial inhibition is considered an important strategy in the search for neuroprotect...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-013-8474-y
更新日期:2013-12-01 00:00:00
abstract::Long-term potentiation (LTP) is a cellular model for learning and memory and believed to be critical for plastic changes in the brain. Depending on the central nervous system region, LTP has been proposed to contribute to many key physiological functions and pathological conditions, such as learning/memory, chronic pa...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-009-8085-9
更新日期:2009-12-01 00:00:00
abstract::Inhibition of potassium channels is possibly the first step in the sequence of biochemical events leading to memory formation. These channels appear to be regulated directly or indirectly by GTP-binding proteins (G proteins), which may themselves be affected by phosphorylation and dephosphorylation in response to elev...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02935554
更新日期:1991-01-01 00:00:00