Abstract：
:Duplication 15q syndrome (Dup15q) is an autism-associated disorder co-incident with high rates of pediatric epilepsy. Additional copies of the E3 ubiquitin ligase UBE3A are thought to cause Dup15q phenotypes, yet models overexpressing UBE3A in neurons have not recapitulated the epilepsy phenotype. We show that Drosophila endogenously expresses Dube3a (fly UBE3A homolog) in glial cells and neurons, prompting an investigation into the consequences of glial Dube3a overexpression. Here we expand on previous work showing that the Na+/K+ pump ATPα is a direct ubiquitin ligase substrate of Dube3a. A robust seizure-like phenotype was observed in flies overexpressing Dube3a in glial cells, but not neurons. Glial-specific knockdown of ATPα also produced seizure-like behavior, and this phenotype was rescued by simultaneously overexpressing ATPα and Dube3a in glia. Our data provides the basis of a paradigm shift in Dup15q research given that clinical phenotypes have long been assumed to be due to neuronal UBE3A overexpression.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Hope KA,LeDoux MS,Reiter LTdoi
10.1016/j.nbd.2017.09.003subject
Has Abstractpub_date
2017-12-01 00:00:00pages
238-248eissn
0969-9961issn
1095-953Xpii
S0969-9961(17)30213-9journal_volume
108pub_type
杂志文章abstract：:Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized behaviorally by chorea, incoordination, and shortened lifespan and neuropathologically by huntingtin inclusions and neuronal degeneration. In order to facilitate studies of pathogenesis and therapeutics, we have generated a new...
journal_title：Neurobiology of disease
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abstract：:Microglia, a type of immune cell in the brain, are in a ramified status with branched processes in normal conditions. Upon pathological stimulation, microglia retract their processes and become activated. Searching methods to make the activated microglia return to ramified status would help cope with injuries induced ...
journal_title：Neurobiology of disease
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journal_title：Neurobiology of disease
pub_type： 杂志文章
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journal_title：Neurobiology of disease
pub_type： 杂志文章
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journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2020.104865
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abstract：:While much of the research on neurodegenerative diseases has focused on neurons, non-neuronal cells are also affected. The extent to which glia and other non-neuronal cells are causally involved in disease pathogenesis versus more passively responding to disease is an area of active research. This is complicated by th...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
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journal_title：Neurobiology of disease
pub_type： 杂志文章
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abstract：:Amyotrophic lateral sclerosis (ALS) is a fatal disease of unknown etiology. Mutations in copper/zinc superoxide dismutase (SOD1) are the most commonly associated genetic abnormality. Given that SOD1 is ubiquitously expressed, the exclusive vulnerability of motor neurons is one of the most puzzling issues in ALS resear...
journal_title：Neurobiology of disease
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doi：10.1016/j.nbd.2006.03.007
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journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2011.08.022
更新日期：2012-01-01 00:00:00
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journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2006.09.012
更新日期：2007-02-01 00:00:00
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journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2004.06.001
更新日期：2004-10-01 00:00:00
abstract：:Alpha-synuclein containing cellular inclusions are a hallmark of Parkinson Disease, Lewy Body Dementia, and Multiple System Atrophy. A genome wide expression screen was performed in C. elegans overexpressing both wild-type and A53T human alpha-synuclein. 433 genes were up- and 67 genes down-regulated by statistical an...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2005.12.021
更新日期：2006-06-01 00:00:00
abstract：:Butyrylcholinesterase (BChE) genotypes and protein (BuChE) activity, especially in combination with Apolipoprotein E4 (ApoE4), have been investigated as risk factors for developing Alzheimer disease (AD) and may be associated with the rate of progression of cognitive decline. Despite similar pathologic (e.g. amyloid d...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2009.05.014
更新日期：2009-08-01 00:00:00
abstract：:Since aberrant miRNA expression has been implicated in numerous brain diseases, we studied miRNA expression and miRNA regulation of important signaling pathways during temporal lobe epileptogenesis in order to identify possible targets for epilepsy therapy. The temporal profile of miRNA expression was analyzed in thre...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2013.10.026
更新日期：2014-02-01 00:00:00
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journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2008.06.002
更新日期：2008-10-01 00:00:00
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journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2016.01.003
更新日期：2016-04-01 00:00:00
abstract：:Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expansion of a CAG repeat in the huntingtin (htt) gene, which results in an aberrant form of the protein (mhtt). This leads to motor and cognitive deficits associated with corticostriatal and hippocampal alterations. The levels of STriat...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.08.024
更新日期：2018-12-01 00:00:00
abstract：:Familial amyotrophic lateral sclerosis (FALS) has been modeled in transgenic mice by introducing mutated versions of human genomic DNA encompassing the entire gene for Cu,Zn superoxide dismutase (SOD1). In this setting, the transgene is expressed throughout the body and results in mice that faithfully recapitulate man...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2005.06.005
更新日期：2005-12-01 00:00:00
abstract：:Mutations in APP (amyloid precursor protein), PSEN1 (presenilin 1) or PSEN2 (presenilin 2) are the main cause of early-onset familial forms of Alzheimer's disease (autosomal dominant AD or ADAD). These genes affect γ-secretase-dependent generation of Amyloid β (Aβ) peptides, the main constituent of amyloid plaques and...
journal_title：Neurobiology of disease
pub_type： 杂志文章
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abstract：:The optic nerve crush injury is a well-accepted model to study the mechanisms of axonal regeneration after trauma in the CNS. The infection of retinal ganglion cells (RGCs) with an adeno-associated virus serotype 2 - ciliary neurotrophic factor (AAV2.CNTF) was previously shown to stimulate axonal regeneration. However...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2012.11.011
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abstract：:Expansion of polyglutamine repeats is the cause of at least nine inherited human neurodegenerative disorders, including Huntington's disease (HD). It is widely accepted that deregulation of the transcriptional coactivator CBP by expanded huntingtin (htt) plays an important role in HD molecular pathogenesis. In this st...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2012.03.008
更新日期：2012-06-01 00:00:00
abstract：:The interplay between excitatory and inhibitory circuits underlies the brain's processes and their dysregulation has been linked to cognitive decline, psychiatric disorders and epilepsy. In patients with Alzheimer's disease (AD), an elevated occurrence of seizures has been observed in both sporadic and familial forms ...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2019.04.010
更新日期：2019-07-01 00:00:00
abstract：:Stimulation of the nicotinic alpha7 acetylcholine receptor (nAChRalpha7) by nicotine or acetylcholine initiates the cholinergic anti-inflammatory pathway, a mechanism for neural inhibition of inflammation. The action of this pathway was initially discovered in animal models of endotoxemia and septic shock, and later d...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2009.03.010
更新日期：2009-07-01 00:00:00
abstract：:Pathological gambling (PG) represents a behavioral side effect of dopamine replacement therapy in a minority of patients with Parkinson's disease (PD). Using striatal dopamine transporter (DAT) with single photon emission tomography we assessed presynaptic dopaminergic function in 8 PD patients with PG, 21 matched PD ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2010.03.013
更新日期：2010-07-01 00:00:00
abstract：:Metabotropic glutamate receptor 5 (mGluR5) is a drug target for central nervous system disorders such as fragile X syndrome that involve excessive glutamate-induced excitation. We tested the efficacy of a novel negative allosteric modulator of mGluR5 developed by Merz Pharmaceuticals, MRZ-8456, in comparison to MPEP a...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.08.008
更新日期：2018-11-01 00:00:00
abstract：:There is evidence that cognitive decline in Alzheimer's disease (AD) results from deficiencies in synaptic communication (e.g., loss of mushroom-shaped 'memory spines') and neurodegenerative processes. This might be treated with sigma-1 receptor (S1R) agonists, which are broadly neuroprotective and modulate synaptic p...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.12.022
更新日期：2019-04-01 00:00:00
abstract：:Immunization of mouse models of Alzheimer disease (AD) with amyloid-peptide (Abeta) reduces Abeta deposits and attenuates their memory and learning deficits. Recent clinical trials were halted due to meningoencephalitis, presumably induced by T cell mediated and/or Fc-mediated immune responses. Because injection of an...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2006.04.012
更新日期：2006-09-01 00:00:00
abstract：:Astrocytes are abundant neuron-supporting glial cells that harbor a powerful arsenal of neuroprotective antioxidative molecules and neurotrophic factors. Here we examined whether enrichment with healthy striatal astrocytes can provide neuroprotection against progressive dopaminergic neurodegeneration. Serotonin 1A (5-...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2013.08.003
更新日期：2013-11-01 00:00:00
abstract：:Transglutaminase 2 (TG2) is a multifunctional protein that modulates cell survival and death pathways. It is upregulated in numerous ischemic models, and protects primary neurons from oxygen and glucose deprivation. TG2 binds to the hypoxia inducible factor (HIF) 1beta and decreases the upregulation of hypoxic-induced...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2010.04.018
更新日期：2010-09-01 00:00:00
abstract：:Several neurodegenerative diseases like Huntington's, a polyglutamine (PolyQ) disease, are initiated by protein aggregation in neurons. Furthermore, these diseases are also associated with a multitude of responses in non-neuronal cells in the brain, in particular glial cells, like astrocytes. These non-neuronal respon...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.10.017
更新日期：2019-04-01 00:00:00
