当前位置： SCI文献检索 > MOLECULAR PSYCHIATRY期刊下所有文献 > Sphingomyelin-induced inhibition of the plasma membrane calcium ATPase causes neurodegeneration in type A Niemann-Pick disease.

Sphingomyelin-induced inhibition of the plasma membrane calcium ATPase causes neurodegeneration in type A Niemann-Pick disease.

Abstract：

:Niemann-Pick disease type A (NPA) is a rare lysosomal storage disorder characterized by severe neurological alterations that leads to death in childhood. Loss-of-function mutations in the acid sphingomyelinase (ASM) gene cause NPA, and result in the accumulation of sphingomyelin (SM) in lysosomes and plasma membrane of neurons. Using ASM knockout (ASMko) mice as a NPA disease model, we investigated how high SM levels contribute to neural pathology in NPA. We found high levels of oxidative stress both in neurons from these mice and a NPA patient. Impaired activity of the plasma membrane calcium ATPase (PMCA) increases intracellular calcium. SM induces PMCA decreased activity, which causes oxidative stress. Incubating ASMko-cultured neurons in the histone deacetylase inhibitor, SAHA, restores PMCA activity and calcium homeostasis and, consequently, reduces the increased levels of oxidative stress. No recovery occurs when PMCA activity is pharmacologically impaired or genetically inhibited in vitro. Oral administration of SAHA prevents oxidative stress and neurodegeneration, and improves behavioral performance in ASMko mice. These results demonstrate a critical role for plasma membrane SM in neuronal calcium regulation. Thus, we identify changes in PMCA-triggered calcium homeostasis as an upstream mediator for NPA pathology. These findings can stimulate new approaches for pharmacological remediation in a disease with no current clinical treatments.

journal_name

Mol Psychiatry

journal_title

Molecular psychiatry

authors

Pérez-Cañamás A,Benvegnù S,Rueda CB,Rábano A,Satrústegui J,Ledesma MD

doi

10.1038/mp.2016.148

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

711-723

issue

5

eissn

1359-4184

issn

1476-5578

pii

mp2016148

journal_volume

22

pub_type

杂志文章

相关文献

MOLECULAR PSYCHIATRY文献大全
  • Polygenic risk for autism, attention-deficit hyperactivity disorder, schizophrenia, major depressive disorder, and neuroticism is associated with the experience of childhood abuse.

    abstract：:People who experience childhood abuse are at increased risk of mental illness. Twin studies suggest that inherited genetic risk for mental illness may account for some of these associations. Yet, the hypothesis that individuals who have experienced childhood abuse may carry genetic loading for mental illness has never...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/s41380-020-00996-w

    authors： Ratanatharathorn A,Koenen KC,Chibnik LB,Weisskopf MG,Rich-Edwards JW,Roberts AL

    更新日期：2021-01-22 00:00:00

  • A CNS-permeable Hsp90 inhibitor rescues synaptic dysfunction and memory loss in APP-overexpressing Alzheimer's mouse model via an HSF1-mediated mechanism.

    abstract：:Induction of neuroprotective heat-shock proteins via pharmacological Hsp90 inhibitors is currently being investigated as a potential treatment for neurodegenerative diseases. Two major hurdles for therapeutic use of Hsp90 inhibitors are systemic toxicity and limited central nervous system permeability. We demonstrate ...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/mp.2016.104

    authors： Wang B,Liu Y,Huang L,Chen J,Li JJ,Wang R,Kim E,Chen Y,Justicia C,Sakata K,Chen H,Planas A,Ostrom RS,Li W,Yang G,McDonald MP,Chen R,Heck DH,Liao FF

    更新日期：2017-07-01 00:00:00

  • Copy number variation in schizophrenia in Sweden.

    abstract：:Schizophrenia (SCZ) is a highly heritable neuropsychiatric disorder of complex genetic etiology. Previous genome-wide surveys have revealed a greater burden of large, rare copy number variations (CNVs) in SCZ cases and identified multiple rare recurrent CNVs that increase risk of SCZ although with incomplete penetranc...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/mp.2014.40

    authors： Szatkiewicz JP,O'Dushlaine C,Chen G,Chambert K,Moran JL,Neale BM,Fromer M,Ruderfer D,Akterin S,Bergen SE,Kähler A,Magnusson PK,Kim Y,Crowley JJ,Rees E,Kirov G,O'Donovan MC,Owen MJ,Walters J,Scolnick E,Sklar P,Pu

    更新日期：2014-07-01 00:00:00

  • Liposome-based targeting of dopamine to the brain: a novel approach for the treatment of Parkinson's disease.

    abstract：:Delivery of drugs into the brain is poor due to the blood brain barrier (BBB). This study describes the development of a novel liposome-based brain-targeting drug delivery system. The liposomes incorporate a diacylglycerol moiety coupled through a linker to a peptide of 5 amino acids selected from amyloid precursor pr...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/s41380-020-0742-4

    authors： Kahana M,Weizman A,Gabay M,Loboda Y,Segal-Gavish H,Gavish A,Barhum Y,Offen D,Finberg J,Allon N,Gavish M

    更新日期：2020-05-05 00:00:00

  • Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability.

    abstract：:Impulsivity, a multifaceted behavioral hallmark of attention-deficit/hyperactivity disorder (ADHD), strongly influences addiction vulnerability and other psychiatric disorders that incur enormous medical and societal burdens yet the neurobiological underpinnings linking impulsivity to disease remain poorly understood....

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/mp.2017.80

    authors： Miller ML,Ren Y,Szutorisz H,Warren NA,Tessereau C,Egervari G,Mlodnicka A,Kapoor M,Chaarani B,Morris CV,Schumann G,Garavan H,Goate AM,Bannon MJ,IMAGEN Consortium.,Halperin JM,Hurd YL

    更新日期：2018-05-01 00:00:00

  • GSK3β negatively regulates TRAX, a scaffold protein implicated in mental disorders, for NHEJ-mediated DNA repair in neurons.

    abstract：:Translin-associated protein X (TRAX) is a scaffold protein with various functions and has been associated with mental illnesses, including schizophrenia. We have previously demonstrated that TRAX interacts with a Gsα protein-coupled receptor, the A2A adenosine receptor (A2AR), and mediates the function of this recepto...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/s41380-017-0007-z

    authors： Chien T,Weng YT,Chang SY,Lai HL,Chiu FL,Kuo HC,Chuang DM,Chern Y

    更新日期：2018-12-01 00:00:00

  • Time-delimited signaling of MET receptor tyrosine kinase regulates cortical circuit development and critical period plasticity.

    abstract：:Normal development of cortical circuits, including experience-dependent cortical maturation and plasticity, requires precise temporal regulation of gene expression and molecular signaling. Such regulation, and the concomitant impact on plasticity and critical periods, is hypothesized to be disrupted in neurodevelopmen...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/s41380-019-0635-6

    authors： Chen K,Ma X,Nehme A,Wei J,Cui Y,Cui Y,Yao D,Wu J,Anderson T,Ferguson D,Levitt P,Qiu S

    更新日期：2020-01-03 00:00:00

  • Molecular interaction between type 2 diabetes and Alzheimer's disease through cross-seeding of protein misfolding.

    abstract：:Numerous epidemiological studies have shown a significantly higher risk for development of Alzheimer's disease (AD) in patients affected by type 2 diabetes (T2D), but the molecular mechanism responsible for this association is presently unknown. Both diseases are considered protein misfolding disorders associated with...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/mp.2016.230

    authors： Moreno-Gonzalez I,Edwards Iii G,Salvadores N,Shahnawaz M,Diaz-Espinoza R,Soto C

    更新日期：2017-09-01 00:00:00

  • Baseline brain structural and functional predictors of clinical outcome in the early course of schizophrenia.

    abstract：:Although schizophrenia is considered a brain disorder, the role of brain organization for symptomatic improvement remains inadequately defined. We investigated the relationship between baseline brain morphology, resting-state network connectivity and clinical response after 24-weeks of antipsychotic treatment in patie...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/s41380-018-0269-0

    authors： Doucet GE,Moser DA,Luber MJ,Leibu E,Frangou S

    更新日期：2020-04-01 00:00:00

  • Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

    abstract：:Bipolar disorder is a major medical, social and economic burden worldwide. However, the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review studies using a neuropharmacological approach in unanesthetized rats, combined with kinetic, biochemical and molecular biology te...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章,评审

    doi：10.1038/mp.2008.31

    authors： Rao JS,Lee HJ,Rapoport SI,Bazinet RP

    更新日期：2008-06-01 00:00:00

  • Neurodevelopmental effects of prenatal vitamin D in humans: systematic review and meta-analysis.

    abstract：:Diverse studies have investigated the impact of prenatal exposure to vitamin D levels on brain development; however, evidence in humans has never been systematically reviewed. This article summarized evidence of the association between 25-hydroxyvitamin D [25(OH)D] levels in maternal blood in pregnancy or newborn bloo...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/s41380-019-0357-9

    authors： García-Serna AM,Morales E

    更新日期：2020-10-01 00:00:00

  • Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial.

    abstract：:Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiological and clinical effects of l-methylfolate, the fully reduced and bioactive form of folate, in schizo...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章,随机对照试验

    doi：10.1038/mp.2017.41

    authors： Roffman JL,Petruzzi LJ,Tanner AS,Brown HE,Eryilmaz H,Ho NF,Giegold M,Silverstein NJ,Bottiglieri T,Manoach DS,Smoller JW,Henderson DC,Goff DC

    更新日期：2018-02-01 00:00:00

  • Cocaine and sucrose rewards recruit different seeking ensembles in the nucleus accumbens core.

    abstract：:Poorly regulated reward seeking is a central feature of substance use disorder. Recent research shows that rewarding drug-related experiences induce synchronous activation of a discrete number of neurons in the nucleus accumbens that are causally linked to reward-related contexts. Here we comprehensively characterize ...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/s41380-020-00888-z

    authors： Bobadilla AC,Dereschewitz E,Vaccaro L,Heinsbroek JA,Scofield MD,Kalivas PW

    更新日期：2020-12-01 00:00:00

  • Effects of oral contraceptive pills on mood and magnetic resonance imaging measures of prefrontal cortical thickness.

    abstract：:Gonadal hormones influence neuronal organization and plasticity. Yet the consequences of altering their concentrations by administering contraceptive agents, which are used by most reproductive-age women in the United States, are unclear. Cross-sectional studies have found both larger and smaller cortical regions alon...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/s41380-020-00990-2

    authors： Petersen N,Kearley NW,Ghahremani DG,Pochon JB,Fry ME,Rapkin AJ,London ED

    更新日期：2021-01-08 00:00:00

  • HPA axis genetic variation, cortisol and psychosis in major depression.

    abstract：:Genetic variation underlying hypothalamic pituitary adrenal (HPA) axis overactivity in healthy controls (HCs) and patients with severe forms of major depression has not been well explored, but could explain risk for cortisol dysregulation. In total, 95 participants were studied: 40 patients with psychotic major depres...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/mp.2013.129

    authors： Schatzberg AF,Keller J,Tennakoon L,Lembke A,Williams G,Kraemer FB,Sarginson JE,Lazzeroni LC,Murphy GM

    更新日期：2014-02-01 00:00:00

  • Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population.

    abstract：:Cognitive impairment is common among individuals diagnosed with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). It has been suggested that some aspects of intelligence are preserved or even superior in people with ASD compared with controls, but consistent evidence is lacking. Few s...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/mp.2015.12

    authors： Clarke TK,Lupton MK,Fernandez-Pujals AM,Starr J,Davies G,Cox S,Pattie A,Liewald DC,Hall LS,MacIntyre DJ,Smith BH,Hocking LJ,Padmanabhan S,Thomson PA,Hayward C,Hansell NK,Montgomery GW,Medland SE,Martin NG,Wright MJ

    更新日期：2016-03-01 00:00:00

  • What is the cellular source of prostaglandins in the brain in response to systemic inflammation? Facts and controversies.

    abstract：:Circulating inflammatory mediators can signal neurons through a pathway in which cytokine activation of the cells of the blood-brain barrier causes the induction of the nuclear factor kappa B (NF-kappaB), leading to the transcription of target genes, such as the one encoding cyclooxygenase 2 (COX-2), the enzyme that i...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章,评审

    doi：

    authors： Rivest S

    更新日期：1999-11-01 00:00:00

  • High throughput fluorescent CE-SSCP SNP genotyping.

    abstract：:Large numbers of single nucleotide polymorphisms (SNPs) are being identified by several laboratories for the purpose of developing dense genetic maps. Single-strand conformation polymorphism (SSCP) analysis has been widely used as a method for detecting novel sequence variations in PCR products. Differences in migrati...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/sj.mp.4000564

    authors： Gonen D,Veenstra-VanderWeele J,Yang Z,Leventhal B,Cook EH Jr

    更新日期：1999-07-01 00:00:00

  • Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase IIalpha gene (PIP5K2A) with schizophrenia.

    abstract：:Linkage studies in schizophrenia have identified a candidate region on chromosome 10p14-11 as reported for several independent samples. We investigated association of DNA sequence variants in a plausible candidate gene located in this region, the gene for phosphatidylinositol-4-phosphate 5-kinase IIalpha (PIP5K2A), in...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章,多中心研究

    doi：10.1038/sj.mp.4001864

    authors： Schwab SG,Knapp M,Sklar P,Eckstein GN,Sewekow C,Borrmann-Hassenbach M,Albus M,Becker T,Hallmayer JF,Lerer B,Maier W,Wildenauer DB

    更新日期：2006-09-01 00:00:00

  • Altered connections on the road to psychopathy.

    abstract：:Psychopathy is strongly associated with serious criminal behaviour (for example, rape and murder) and recidivism. However, the biological basis of psychopathy remains poorly understood. Earlier studies suggested that dysfunction of the amygdala and/or orbitofrontal cortex (OFC) may underpin psychopathy. Nobody, howeve...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/mp.2009.40

    authors： Craig MC,Catani M,Deeley Q,Latham R,Daly E,Kanaan R,Picchioni M,McGuire PK,Fahy T,Murphy DG

    更新日期：2009-10-01 00:00:00

  • The phenotypes of bipolar disorder: relevance for genetic investigations.

    abstract：:The search for susceptibility genes for bipolar disorder (BD) depends on appropriate definitions of the phenotype. In this paper, we review data on diagnosis and clinical features of BD that could be used in genetic studies to better characterize patients or to define homogeneous subgroups. Clinical symptoms, long-ter...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章,评审

    doi：10.1038/sj.mp.4001701

    authors： MacQueen GM,Hajek T,Alda M

    更新日期：2005-09-01 00:00:00

  • Prevention of schizophrenia deficits via non-invasive adolescent frontal cortex stimulation in rats.

    abstract：:Schizophrenia is a severe neurodevelopmental psychiatric affliction manifested behaviorally at late adolescence/early adulthood. Current treatments comprise antipsychotics which act solely symptomatic, are limited in their effectiveness and often associated with side-effects. We here report that application of non-inv...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/s41380-019-0356-x

    authors： Hadar R,Winter R,Edemann-Callesen H,Wieske F,Habelt B,Khadka N,Felgel-Farnholz V,Barroeta-Hlusicka E,Reis J,Tatarau CA,Funke K,Fritsch B,Bernhardt N,Bikson M,Nitsche MA,Winter C

    更新日期：2020-04-01 00:00:00

  • Muscarinic1 and 2 receptor mRNA in the human caudate-putamen: no change in m1 mRNA in schizophrenia.

    abstract：:Studies using tissue obtained at autopsy suggest that changes in cholinergic neurons could be important in the pathology of schizophrenia.1-4 We have previously reported a decrease in [3H]pirenzepine binding5 and [3H]AF-DX 384 binding6 to caudate-putamen (CP) from subjects who had schizophrenia. Under the conditions c...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/sj.mp.4000684

    authors： Dean B,Crook JM,Pavey G,Opeskin K,Copolov DL

    更新日期：2000-03-01 00:00:00

  • The absence of VGLUT3 predisposes to cocaine abuse by increasing dopamine and glutamate signaling in the nucleus accumbens.

    abstract：:Tonically active cholinergic interneurons (TANs) from the nucleus accumbens (NAc) are centrally involved in reward behavior. TANs express a vesicular glutamate transporter referred to as VGLUT3 and thus use both acetylcholine and glutamate as neurotransmitters. The respective roles of each transmitter in the regulatio...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/mp.2015.104

    authors： Sakae DY,Marti F,Lecca S,Vorspan F,Martín-García E,Morel LJ,Henrion A,Gutiérrez-Cuesta J,Besnard A,Heck N,Herzog E,Bolte S,Prado VF,Prado MA,Bellivier F,Eap CB,Crettol S,Vanhoutte P,Caboche J,Gratton A,Moquin L,

    更新日期：2015-11-01 00:00:00

  • Modeling the functional genomics of autism using human neurons.

    abstract：:Human neural progenitors from a variety of sources present new opportunities to model aspects of human neuropsychiatric disease in vitro. Such in vitro models provide the advantages of a human genetic background combined with rapid and easy manipulation, making them highly useful adjuncts to animal models. Here, we ex...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/mp.2011.60

    authors： Konopka G,Wexler E,Rosen E,Mukamel Z,Osborn GE,Chen L,Lu D,Gao F,Gao K,Lowe JK,Geschwind DH

    更新日期：2012-02-01 00:00:00

  • CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders.

    abstract：:Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact....

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/mp.2016.61

    authors： Mercati O,Huguet G,Danckaert A,André-Leroux G,Maruani A,Bellinzoni M,Rolland T,Gouder L,Mathieu A,Buratti J,Amsellem F,Benabou M,Van-Gils J,Beggiato A,Konyukh M,Bourgeois JP,Gazzellone MJ,Yuen RK,Walker S,Delépine M

    更新日期：2017-04-01 00:00:00

  • Educational attainment and drinking behaviors: Mendelian randomization study in UK Biobank.

    abstract：:Educational attainment has been associated with drinking behaviors in observation studies. We performed Mendelian randomization analysis to determine whether educational attainment causally affected drinking behaviors, including amount of alcohol intakes (in total and various types), drinking frequency, and drinking w...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/s41380-019-0596-9

    authors： Zhou T,Sun D,Li X,Ma H,Heianza Y,Qi L

    更新日期：2019-11-25 00:00:00

  • Transgenic modeling of neuropsychiatric disorders.

    abstract：:Converging advances in the fields of molecular biology, molecular genetics, cellular biology and embryology have given researchers the tools for the targeted delivery and stable germline transmission of foreign genes (transgenes) in the mouse. In the realm of neuropsychiatry, this so-named transgenic technology has be...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章,评审

    doi：

    authors： Campbell IL,Gold LH

    更新日期：1996-05-01 00:00:00

  • Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study.

    abstract：:Endocannabinoids and their attending cannabinoid type 1 (CB1) receptor have been implicated in animal models of post-traumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/mp.2013.61

    authors： Neumeister A,Normandin MD,Pietrzak RH,Piomelli D,Zheng MQ,Gujarro-Anton A,Potenza MN,Bailey CR,Lin SF,Najafzadeh S,Ropchan J,Henry S,Corsi-Travali S,Carson RE,Huang Y

    更新日期：2013-09-01 00:00:00

  • Serotonin transporter polymorphism, memory and hippocampal volume in the elderly: association and interaction with cortisol.

    abstract：:The s allele variant of the serotonin transporter gene (5-HTT) has recently been observed to moderate the relationship of stress to depression and anxiety. To date no study has considered interactive effects of 5-HTT genotype, stress and hypothalamic-pituitary-adrenal (HPA) function on cognition in healthy, older adul...

    journal_title：Molecular psychiatry

    pub_type： 杂志文章

    doi：10.1038/sj.mp.4001978

    authors： O'Hara R,Schröder CM,Mahadevan R,Schatzberg AF,Lindley S,Fox S,Weiner M,Kraemer HC,Noda A,Lin X,Gray HL,Hallmayer JF

    更新日期：2007-06-01 00:00:00