Translating glutamate: from pathophysiology to treatment.

Abstract:

:The neurotransmitter glutamate is the primary excitatory neurotransmitter in mammalian brain and is responsible for most corticocortical and corticofugal neurotransmission. Disturbances in glutamatergic function have been implicated in the pathophysiology of several neuropsychiatric disorders-including schizophrenia, drug abuse and addiction, autism, and depression-that were until recently poorly understood. Nevertheless, improvements in basic information regarding these disorders have yet to translate into Food and Drug Administration-approved treatments. Barriers to translation include the need not only for improved compounds but also for improved biomarkers sensitive to both structural and functional target engagement and for improved translational models. Overcoming these barriers will require unique collaborative arrangements between pharma, government, and academia. Here, we review a recent Institute of Medicine-sponsored meeting, highlighting advances in glutamatergic theories of neuropsychiatric illness as well as remaining barriers to treatment development.

journal_name

Sci Transl Med

authors

Javitt DC,Schoepp D,Kalivas PW,Volkow ND,Zarate C,Merchant K,Bear MF,Umbricht D,Hajos M,Potter WZ,Lee CM

doi

10.1126/scitranslmed.3002804

subject

Has Abstract

pub_date

2011-09-28 00:00:00

pages

102mr2

issue

102

eissn

1946-6234

issn

1946-6242

pii

3/102/102mr2

journal_volume

3

pub_type

杂志文章,评审
  • Epidermal EGFR controls cutaneous host defense and prevents inflammation.

    abstract::The epidermal growth factor receptor (EGFR) plays an important role in tissue homeostasis and tumor progression. However, cancer patients treated with EGFR inhibitors (EGFRIs) frequently develop acneiform skin toxicities, which are a strong predictor of a patient's treatment response. We show that the early inflammato...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3005886

    authors: Lichtenberger BM,Gerber PA,Holcmann M,Buhren BA,Amberg N,Smolle V,Schrumpf H,Boelke E,Ansari P,Mackenzie C,Wollenberg A,Kislat A,Fischer JW,Röck K,Harder J,Schröder JM,Homey B,Sibilia M

    更新日期:2013-08-21 00:00:00

  • Sponsors meet scientists to speed pediatric medicines development.

    abstract::The Point-Person Project, a child-health research initiative, enables rapid response to opportunities for participation in multicenter pediatric clinical trials. ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaa2045

    authors: Davis JM,Smoyer WE,Connor EM,Huskins WC,Pastern C,Purucker M,Schrader EC,Jackson CR,Kaskel FJ,Hirschfeld S

    更新日期:2015-03-18 00:00:00

  • Preclinical and clinical assessment of inhaled levodopa for OFF episodes in Parkinson's disease.

    abstract::Inhaled drugs offer advantages, such as rapid onset of action, but require formulations and delivery systems that reproducibly and conveniently administer the drug. CVT-301 is a powder formulation of levodopa delivered by a breath-actuated inhaler that has been developed for treating OFF episodes (motor fluctuations b...

    journal_title:Science translational medicine

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1126/scitranslmed.aad8858

    authors: Lipp MM,Batycky R,Moore J,Leinonen M,Freed MI

    更新日期:2016-10-12 00:00:00

  • Liberating health data for clinical research applications.

    abstract::Global investments in health information technology (HIT) in the form of electronic health record systems represent important new strategies to improve the quality and efficiency of health care. These potential benefits of HIT will not be achieved without direct attention to the use of health care information for clin...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000764

    authors: Nadler JJ,Downing GJ

    更新日期:2010-02-10 00:00:00

  • Curative ex vivo liver-directed gene therapy in a pig model of hereditary tyrosinemia type 1.

    abstract::We tested the hypothesis that ex vivo hepatocyte gene therapy can correct the metabolic disorder in fumarylacetoacetate hydrolase-deficient (Fah(-/-)) pigs, a large animal model of hereditary tyrosinemia type 1 (HT1). Recipient Fah(-/-) pigs underwent partial liver resection and hepatocyte isolation by collagenase dig...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaf3838

    authors: Hickey RD,Mao SA,Glorioso J,Elgilani F,Amiot B,Chen H,Rinaldo P,Marler R,Jiang H,DeGrado TR,Suksanpaisan L,O'Connor MK,Freeman BL,Ibrahim SH,Peng KW,Harding CO,Ho CS,Grompe M,Ikeda Y,Lillegard JB,Russell SJ,Nybe

    更新日期:2016-07-27 00:00:00

  • Brief suppression of Abcc8 prevents autodestruction of spinal cord after trauma.

    abstract::Spinal cord injury (SCI) is typically complicated by progressive hemorrhagic necrosis, an autodestructive process of secondary injury characterized by progressive enlargement of a hemorrhagic contusion during the first several hours after trauma. We assessed the role of Abcc8, which encodes sulfonylurea receptor 1 (SU...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000522

    authors: Simard JM,Woo SK,Norenberg MD,Tosun C,Chen Z,Ivanova S,Tsymbalyuk O,Bryan J,Landsman D,Gerzanich V

    更新日期:2010-04-21 00:00:00

  • Parallel discovery of Alzheimer's therapeutics.

    abstract::As the prevalence of Alzheimer's disease (AD) grows, so do the costs it imposes on society. Scientific, clinical, and financial interests have focused current drug discovery efforts largely on the single biological pathway that leads to amyloid deposition. This effort has resulted in slow progress and disappointing ou...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3008228

    authors: Lo AW,Ho C,Cummings J,Kosik KS

    更新日期:2014-06-18 00:00:00

  • A vaccine-induced gene expression signature correlates with protection against SIV and HIV in multiple trials.

    abstract::Current HIV vaccines are only partially efficacious, presenting an opportunity to identify correlates of protection and, thereby, potential insight into mechanisms that prevent HIV acquisition. Two independent preclinical challenge studies in nonhuman primates (NHPs) previously showed partial efficacy of a mosaic aden...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaw4236

    authors: Ehrenberg PK,Shangguan S,Issac B,Alter G,Geretz A,Izumi T,Bryant C,Eller MA,Wegmann F,Apps R,Creegan M,Bolton DL,Sekaly RP,Robb ML,Gramzinski RA,Pau MG,Schuitemaker H,Barouch DH,Michael NL,Thomas R

    更新日期:2019-08-28 00:00:00

  • A molecular bandage for diseased muscle.

    abstract::MG53 promotes sarcolemmal repair in the mdx mouse model of Duchenne muscular dystrophy (Weisleder et al., this issue) and identifies a new protein therapeutic for muscle disease. ...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.3004082

    authors: Burkin DJ,Wuebbles RD

    更新日期:2012-06-20 00:00:00

  • The gracefully aging immune system.

    abstract::Prolonged life expectancy in the 20th century has been one of humankind's greatest triumphs. However, the substantial increase in the human life span has ushered in a new concern: healthy aging. Because infectious diseases prominently contribute to morbidity in the particularly vulnerable elderly population, strategie...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.3005624

    authors: Boraschi D,Aguado MT,Dutel C,Goronzy J,Louis J,Grubeck-Loebenstein B,Rappuoli R,Del Giudice G

    更新日期:2013-05-15 00:00:00

  • Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis.

    abstract::Patients with rheumatoid arthritis (RA) may display atypical CD21-/lo B cells in their blood, but the implication of this observation remains unclear. We report here that the group of patients with RA and elevated frequencies of CD21-/lo B cells shows decreased ataxia telangiectasia-mutated (ATM) expression and activa...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaw4626

    authors: Mensah KA,Chen JW,Schickel JN,Isnardi I,Yamakawa N,Vega-Loza A,Anolik JH,Gatti RA,Gelfand EW,Montgomery RR,Horowitz MC,Craft JE,Meffre E

    更新日期:2019-11-20 00:00:00

  • Designing a public square for research computing.

    abstract::A set of principles is proposed for sponsors and developers of research computing applications that can increase the likelihood of successful adoption by researchers. ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3004032

    authors: Masys DR,Harris PA,Fearn PA,Kohane IS

    更新日期:2012-08-29 00:00:00

  • Wnt proteins promote bone regeneration.

    abstract::The Wnt signaling pathway plays a central role in bone development and homeostasis. In most cases, Wnt ligands promote bone growth, which has led to speculation that Wnt factors could be used to stimulate bone healing. We gained insights into the mechanism by which Wnt signaling regulates adult bone repair through the...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000231

    authors: Minear S,Leucht P,Jiang J,Liu B,Zeng A,Fuerer C,Nusse R,Helms JA

    更新日期:2010-04-28 00:00:00

  • Photoactivation of endogenous latent transforming growth factor-β1 directs dental stem cell differentiation for regeneration.

    abstract::Rapid advancements in the field of stem cell biology have led to many current efforts to exploit stem cells as therapeutic agents in regenerative medicine. However, current ex vivo cell manipulations common to most regenerative approaches create a variety of technical and regulatory hurdles to their clinical translati...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3008234

    authors: Arany PR,Cho A,Hunt TD,Sidhu G,Shin K,Hahm E,Huang GX,Weaver J,Chen AC,Padwa BL,Hamblin MR,Barcellos-Hoff MH,Kulkarni AB,J Mooney D

    更新日期:2014-05-28 00:00:00

  • Plasmacytoid dendritic cells, interferon signaling, and FcγR contribute to pathogenesis and therapeutic response in childhood immune thrombocytopenia.

    abstract::Immune thrombocytopenia (ITP) is an autoimmune disorder of childhood characterized by immune-mediated destruction of platelets. The mechanisms underlying the pathogenesis of ITP and the therapeutic efficacy of intravenous immunoglobulins (IVIG) in this disorder remain unclear. We show that monocytes from patients with...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3006277

    authors: Sehgal K,Guo X,Koduru S,Shah A,Lin A,Yan X,Dhodapkar KM

    更新日期:2013-07-10 00:00:00

  • Impact of guidance documents on translational large animal studies of cartilage repair.

    abstract::Promising therapies for cartilage repair are translated through large animal models toward human application. To guide this work, regulatory agencies publish recommendations ("guidance documents") to direct pivotal large animal studies. These are meant to aid in study design, outline metrics for judging efficacy, and ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aac7019

    authors: Pfeifer CG,Fisher MB,Carey JL,Mauck RL

    更新日期:2015-10-21 00:00:00

  • Tmc gene therapy restores auditory function in deaf mice.

    abstract::Genetic hearing loss accounts for up to 50% of prelingual deafness worldwide, yet there are no biologic treatments currently available. To investigate gene therapy as a potential biologic strategy for restoration of auditory function in patients with genetic hearing loss, we tested a gene augmentation approach in mous...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aab1996

    authors: Askew C,Rochat C,Pan B,Asai Y,Ahmed H,Child E,Schneider BL,Aebischer P,Holt JR

    更新日期:2015-07-08 00:00:00

  • Aggregate penetrance of genomic variants for actionable disorders in European and African Americans.

    abstract::In populations that have not been selected for family history of disease, it is unclear how commonly pathogenic variants (PVs) in disease-associated genes for rare Mendelian conditions are found and how often they are associated with clinical features of these conditions. We conducted independent, prospective analyses...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aag2367

    authors: Natarajan P,Gold NB,Bick AG,McLaughlin H,Kraft P,Rehm HL,Peloso GM,Wilson JG,Correa A,Seidman JG,Seidman CE,Kathiresan S,Green RC

    更新日期:2016-11-09 00:00:00

  • A bifunctional nociceptin and mu opioid receptor agonist is analgesic without opioid side effects in nonhuman primates.

    abstract::Misuse of prescription opioids, opioid addiction, and overdose underscore the urgent need for developing addiction-free effective medications for treating severe pain. Mu opioid peptide (MOP) receptor agonists provide very effective pain relief. However, severe side effects limit their use in the clinical setting. Ago...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aar3483

    authors: Ding H,Kiguchi N,Yasuda D,Daga PR,Polgar WE,Lu JJ,Czoty PW,Kishioka S,Zaveri NT,Ko MC

    更新日期:2018-08-29 00:00:00

  • The Src/c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis.

    abstract::Amyotrophic lateral sclerosis (ALS), a fatal disease causing progressive loss of motor neurons, still has no effective treatment. We developed a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout. Motor neurons were generated from induced pluripotent stem cells (iPSCs) derived fro...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaf3962

    authors: Imamura K,Izumi Y,Watanabe A,Tsukita K,Woltjen K,Yamamoto T,Hotta A,Kondo T,Kitaoka S,Ohta A,Tanaka A,Watanabe D,Morita M,Takuma H,Tamaoka A,Kunath T,Wray S,Furuya H,Era T,Makioka K,Okamoto K,Fujisawa T,Nishit

    更新日期:2017-05-24 00:00:00

  • Rare copy number variation discovery and cross-disorder comparisons identify risk genes for ADHD.

    abstract::Attention deficit hyperactivity disorder (ADHD) is a common and persistent condition characterized by developmentally atypical and impairing inattention, hyperactivity, and impulsiveness. We identified de novo and rare copy number variations (CNVs) in 248 unrelated ADHD patients using million-feature genotyping arrays...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3002464

    authors: Lionel AC,Crosbie J,Barbosa N,Goodale T,Thiruvahindrapuram B,Rickaby J,Gazzellone M,Carson AR,Howe JL,Wang Z,Wei J,Stewart AF,Roberts R,McPherson R,Fiebig A,Franke A,Schreiber S,Zwaigenbaum L,Fernandez BA,Roberts W

    更新日期:2011-08-10 00:00:00

  • Long-term follow-up after gene therapy for canavan disease.

    abstract::Canavan disease is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to loss of enzyme activity and increased concentrations of the substrate N-acetyl-aspartate (NAA) in the brain. Accumulation of NAA results in spongiform degeneration of white matter and severe impairment of p...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3003454

    authors: Leone P,Shera D,McPhee SW,Francis JS,Kolodny EH,Bilaniuk LT,Wang DJ,Assadi M,Goldfarb O,Goldman HW,Freese A,Young D,During MJ,Samulski RJ,Janson CG

    更新日期:2012-12-19 00:00:00

  • Avidity-based binding to HER2 results in selective killing of HER2-overexpressing cells by anti-HER2/CD3.

    abstract::A primary barrier to the success of T cell-recruiting bispecific antibodies in the treatment of solid tumors is the lack of tumor-specific targets, resulting in on-target off-tumor adverse effects from T cell autoreactivity to target-expressing organs. To overcome this, we developed an anti-HER2/CD3 T cell-dependent b...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aat5775

    authors: Slaga D,Ellerman D,Lombana TN,Vij R,Li J,Hristopoulos M,Clark R,Johnston J,Shelton A,Mai E,Gadkar K,Lo AA,Koerber JT,Totpal K,Prell R,Lee G,Spiess C,Junttila TT

    更新日期:2018-10-17 00:00:00

  • Clinical trial design: The nobility of randomization.

    abstract::A clinical trial evaluating HIV vaccine therapy teaches us much about optimal design (Sneller et al, this issue). ...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.aaq0810

    authors: Michael NL

    更新日期:2017-12-06 00:00:00

  • Lactation improves pancreatic β cell mass and function through serotonin production.

    abstract::Pregnancy imposes a substantial metabolic burden on women through weight gain and insulin resistance. Lactation reduces the risk of maternal postpartum diabetes, but the mechanisms underlying this benefit are unknown. Here, we identified long-term beneficial effects of lactation on β cell function, which last for year...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aay0455

    authors: Moon JH,Kim H,Kim H,Park J,Choi W,Choi W,Hong HJ,Ro HJ,Jun S,Choi SH,Banerjee RR,Shong M,Cho NH,Kim SK,German MS,Jang HC,Kim H

    更新日期:2020-04-29 00:00:00

  • Immunoglobulin class-switched B cells form an active immune axis between CNS and periphery in multiple sclerosis.

    abstract::In multiple sclerosis (MS), lymphocyte--in particular B cell--transit between the central nervous system (CNS) and periphery may contribute to the maintenance of active disease. Clonally related B cells exist in the cerebrospinal fluid (CSF) and peripheral blood (PB) of MS patients; however, it remains unclear which s...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3008930

    authors: Palanichamy A,Apeltsin L,Kuo TC,Sirota M,Wang S,Pitts SJ,Sundar PD,Telman D,Zhao LZ,Derstine M,Abounasr A,Hauser SL,von Büdingen HC

    更新日期:2014-08-06 00:00:00

  • Development of personalized tumor biomarkers using massively parallel sequencing.

    abstract::Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. The evaluation of patient-specific translocations in leukemias and lymphomas has revolutionized diagnostics for these diseases. We have developed a method, called personalized analysis of rearranged ends (PARE...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000702

    authors: Leary RJ,Kinde I,Diehl F,Schmidt K,Clouser C,Duncan C,Antipova A,Lee C,McKernan K,De La Vega FM,Kinzler KW,Vogelstein B,Diaz LA Jr,Velculescu VE

    更新日期:2010-02-24 00:00:00

  • Key elements for nourishing the translational research environment.

    abstract::Translation in an academic environment requires a support system--people, goals, models, partnerships, and infrastructures--that will push promising basic science and technology projects forward into the clinic. ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaa2049

    authors: Volk HD,Stevens MM,Mooney DJ,Grainger DW,Duda GN

    更新日期:2015-04-08 00:00:00

  • Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells.

    abstract::Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaw6003

    authors: Peired AJ,Antonelli G,Angelotti ML,Allinovi M,Guzzi F,Sisti A,Semeraro R,Conte C,Mazzinghi B,Nardi S,Melica ME,De Chiara L,Lazzeri E,Lasagni L,Lottini T,Landini S,Giglio S,Mari A,Di Maida F,Antonelli A,Porpiglia F

    更新日期:2020-03-25 00:00:00

  • Assessing the safety of adjuvanted vaccines.

    abstract::Despite the very low risk-to-benefit ratio of vaccines, fear of negative side effects has discouraged many people from getting vaccinated, resulting in reemergence of previously controlled diseases such as measles, pertussis, and diphtheria. Part of this fear stems from the lack of public awareness of the many preclin...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.3002302

    authors: Ahmed SS,Plotkin SA,Black S,Coffman RL

    更新日期:2011-07-27 00:00:00