Abstract:
:Alzheimer's disease (AD) is the most common cause of dementia and is characterized by the buildup of β-amyloid plaques and neurofibrillary Tau tangles. This leads to decreased synaptic efficacy, cell death, and, consequently, brain atrophy in patients. Behaviorally, this manifests as memory loss and confusion. Using a gene ontology analysis, we recently identified AD and other age-related dementias as candidate diseases associated with the loss of DEK expression. DEK is a nuclear phosphoprotein with roles in DNA repair, cellular proliferation, and inhibiting apoptosis. Work from our laboratory determined that DEK is highly expressed in the brain, particularly in regions relevant to learning and memory, including the hippocampus. Moreover, we have also determined that DEK is highly expressed in neurons. Consistent with our gene ontology analysis, we recently reported that cortical DEK protein levels are inversely proportional to dementia severity scores in elderly female patients. However, the functional role of DEK in neurons is unknown. Thus, we knocked down DEK in an in vitro neuronal model, differentiated SH-SY5Y cells, hypothesizing that DEK loss would result in cellular and molecular phenotypes consistent with AD. We found that DEK loss resulted in increased neuronal death by apoptosis (i.e., cleaved caspases 3 and 8), decreased β-catenin levels, disrupted neurite development, higher levels of total and phosphorylated Tau at Ser262, and protein aggregates. We have demonstrated that DEK loss in vitro recapitulates cellular and molecular phenotypes of AD pathology.
journal_name
Front Mol Neuroscijournal_title
Frontiers in molecular neuroscienceauthors
Greene AN,Parks LG,Solomon MB,Privette Vinnedge LMdoi
10.3389/fnmol.2020.594319subject
Has Abstractpub_date
2020-11-16 00:00:00pages
594319issn
1662-5099journal_volume
13pub_type
杂志文章abstract::Parkinson's disease (PD) is a progressive CNS disorder that is primarily associated with impaired movement. PD develops over decades and is linked to the gradual loss of dopamine delivery to the striatum, via the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). While the administration o...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00010
更新日期:2019-02-11 00:00:00
abstract::The anterior cingulate cortex (ACC) is an important brain area for the regulation of neuropathic pain. The α2A adrenoceptor is a good target for pain management. However, the role of cingulate α2A adrenoceptors in the regulation of neuropathic pain has been less studied. In this study, we investigated the involvement ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00289
更新日期:2017-09-12 00:00:00
abstract::The bioactive lipid sphingosine-1-phosphate (S1P) is an important regulator in the nervous system. Here, we explored the role of S1P and its receptors in vitro and in preclinical models of peripheral nerve regeneration. Adult sensory neurons and motor neuron-like cells were exposed to S1P in an in vitro assay, and vir...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00317
更新日期:2017-10-10 00:00:00
abstract::[This corrects the article DOI: 10.3389/fnmol.2018.00312.]. ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,已发布勘误
doi:10.3389/fnmol.2019.00079
更新日期:2019-04-04 00:00:00
abstract::Corticotropin releasing factor (CRF) has been shown to induce various behavioral changes related to adaptation to stress. Dysregulation of the CRF system at any point can lead to a variety of psychiatric disorders, including substance use disorders (SUDs). CRF has been associated with stress-induced drug reinforcement...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2012.00091
更新日期:2012-09-06 00:00:00
abstract::The cells of the neural crest, often referred to as neural crest stem cells, give rise to a number of sub-lineages, one of which is Schwann cells, the glial cells of peripheral nerves. Crest cells transform to adult Schwann cells through the generation of two well defined intermediate stages, the Schwann cell precurso...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2019.00069
更新日期:2019-03-26 00:00:00
abstract::Long non-coding RNAs (lncRNAs) have emerged as an important regulatory control in biological systems. Though the field of lncRNA has been progressing rapidly, a complete understanding of the role of lncRNAs in neuroblastoma pathogenesis is still lacking. To identify the abrogated lncRNAs in primary neuroblastoma and i...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00293
更新日期:2019-12-12 00:00:00
abstract::Kainate (KA) is a potent neurotoxin that has been widely used experimentally to induce acute brain seizures and, after repetitive treatments, as a chronic model of temporal lobe epilepsy (TLE), with similar features to those observed in human patients with TLE. However, whether KA activates KA receptors (KARs) as an a...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2018.00217
更新日期:2018-06-22 00:00:00
abstract::Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. It is caused by the overexpansion of cytosine-guanine-guanine (CGG) trinucleotide in Fmr1 gene, resulting in complete loss of the fragile X mental retardation protein (FMRP). Previous studies using Fmr1 knockout (Fmr1 KO) mice have ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00495
更新日期:2019-01-17 00:00:00
abstract::Sex-determining region Y box 2 (Sox2), expressed in neural tissues, plays an important role as a transcription factor not only in the pluripotency and proliferation of neuronal cells but also in the opposite function of cell differentiation. Nevertheless, how Sox2 is linked to motor neuron development remains unknown....
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.00034
更新日期:2020-03-27 00:00:00
abstract::M/Kv7 potassium channels play a key role in regulation of neuronal excitability. Modulation of neuronal excitability of primary sensory neurons determines the itch sensation induced by a variety of itch-causing substances including chloroquine (CQ). In the present study, we demonstrate that suppression of M/Kv7 channe...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.00105
更新日期:2020-06-30 00:00:00
abstract::MiRNAs are key regulators of the mammalian transcriptome that have been increasingly linked to degenerative diseases of the motor neurons. Although many of the miRNAs currently incriminated as participants in the pathogenesis of these diseases are also important to the normal development and function of motor neurons,...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00127
更新日期:2017-05-04 00:00:00
abstract::Alzheimer's disease (AD) is a progressive disease with early degeneration of the central cholinergic neurons. Currently, three of four AD drugs act by inhibiting the acetylcholine (ACh) degrading enzyme, acetylcholinesterase (AChE). Efficacy of these drugs depends on available amount of ACh, which is biosynthesized by...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00239
更新日期:2019-10-11 00:00:00
abstract::Inhibition of nerve growth and plasticity in the CNS is to a large part mediated by Nogo-like signaling, now encompassing a plethora of ligands, receptors, co-receptors and modulators. Here we describe the distribution and levels of mRNA encoding 11 key genes involved in Nogo-like signaling (Nogo-A, Oligodendrocyte-My...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00094
更新日期:2017-04-11 00:00:00
abstract::Despite numerous clinical studies, which have investigated the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) in various brain diseases, our knowledge of the cellular and molecular mechanisms underlying rTMS-based therapies remains limited. Thus, a deeper understanding of rTMS-induced neu...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2013.00050
更新日期:2013-12-17 00:00:00
abstract::It has been 200 years since Parkinson's disease (PD) was first described, yet many aspects of its etiopathogenesis remain unclear. PD is a progressive and complex neurodegenerative disorder caused by genetic and environmental factors including aging, nutrition, pesticides and exposure to heavy metals. DNA methylation ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00225
更新日期:2017-07-18 00:00:00
abstract::The ubiquitin proteasome system (UPS) is crucial for intracellular protein homeostasis and for degradation of aberrant and damaged proteins. The accumulation of ubiquitinated proteins is a hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, and Huntington's d...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2014.00073
更新日期:2014-08-08 00:00:00
abstract::[This corrects the article on p. 257 in vol. 10, PMID: 28855859.]. ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,已发布勘误
doi:10.3389/fnmol.2017.00392
更新日期:2017-11-20 00:00:00
abstract::Neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA) are chronic, progressive, and age-associated neurological disorders characterized by neuronal deterioration in specific brain regions. Although the specific path...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2019.00141
更新日期:2019-06-05 00:00:00
abstract::Dysfunctions in hearing and balance are largely connected with hair cell (HC) loss. Although regeneration of HCs in the adult cochlea does not occur, there is still limited capacity for HC regeneration in the mammalian utricle from a distinct population of supporting cells (SCs). In response to HC damage, these Lgr5+ ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00137
更新日期:2018-04-30 00:00:00
abstract::This review will consider the impact of compromised PTEN signaling in brain patterning. We approach understanding the contribution of PTEN to nervous system development by surveying the findings from the numerous genetic loss-of-function models that have been generated as well as other forms of PTEN inactivation. By e...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2014.00035
更新日期:2014-05-14 00:00:00
abstract::The ventrolateral hypothalamic parvafox (formerly called PV1-Foxb1) nucleus is an anatomical entity of recent discovery and unknown function. With a view to gaining an insight into its putative functional role(s), we conducted a gene-microarray analysis and, armed with the forthcoming data, controlled the results with...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00008
更新日期:2017-01-23 00:00:00
abstract::Mitochondrial dysfunction is a prominent trait of cellular decline during aging and intimately linked to neuronal degeneration during Parkinson's disease (PD). Various proteins associated with PD have been shown to differentially impact mitochondrial dynamics, quality control and function, including the leucine-rich r...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00205
更新日期:2018-06-21 00:00:00
abstract::Microglial activation and the inflammatory response in the central nervous system (CNS) play important roles in secondary damage after traumatic brain injury (TBI). Transcriptional activation of genes that limit secondary damage to the CNS are mediated by a cis-acting element called the antioxidant responsive element ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00117
更新日期:2018-04-17 00:00:00
abstract::Glycine receptors (GlyRs) containing the α2 subunit are highly expressed in the developing brain, where they regulate neuronal migration and maturation, promote spontaneous network activity and subsequent development of synaptic connections. Mutations in GLRA2 are associated with autism spectrum disorder, but the unde...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00380
更新日期:2018-10-15 00:00:00
abstract::Studies on the association between post-traumatic stress disorder (PTSD) and levels of catecholamines have yielded inconsistent results. The aim of this study was to conduct a systematic review and meta-analysis to assess whether concentrations of the catecholamines dopamine, norepinephrine, and epinephrine are associ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00450
更新日期:2018-12-04 00:00:00
abstract::The post-synaptic density protein 95 (PSD-95) plays a central role in excitatory synapse development and synaptic plasticity. Phosphorylation of the N-terminus of PSD-95 at threonine 19 (T19) and serine 25 (S25) decreases PSD-95 stability at synapses; however, a molecular mechanism linking PSD-95 phosphorylation to al...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.00010
更新日期:2020-03-13 00:00:00
abstract::Potassium chloride co-transporter 2 (KCC2), a major chloride transporter that maintains GABAA receptor inhibition in mature mammalian neurons, is down-regulated in the hippocampus during epileptogenesis. Impaired KCC2 function accelerates or facilitates seizure onset. Calpain, with two main subtypes of m- and μ-calpai...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00287
更新日期:2018-08-21 00:00:00
abstract::There are many unanswered questions about the roles of the actin pointed end capping and actin nucleation by tropomodulins (Tmod) in regulating neural morphology. Previous studies indicate that Tmod1 and Tmod2 regulate morphology of the dendritic arbor and spines. Tmod3, which is expressed in the brain, had only a min...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00357
更新日期:2018-10-09 00:00:00
abstract::The tetrameric capsaicin receptor transient receptor potential vanilloid 1 (TRPV1) in mammals has evolved the capability to integrate pain signal arising from harmful temperature and chemical irritants. The four repetitions of TRPV1 subunits result in an ion channel with excellent pain sensitivity, allowing this ionot...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00302
更新日期:2020-01-09 00:00:00