Cheating Death: New Molecules Block BAX.

Abstract:

:BAX is a formidable BCL-2 family protein that executes cellular suicide in response to physiologic and pathologic stress. A new article in Nature Chemical Biology (Garner et al.https://doi.org/10.1038/s41589-018-0223-0) reports small molecules that inhibit the conformational activation of BAX, informing a pharmacologic approach to blocking unwanted cell death in human disease.

journal_name

Trends Mol Med

authors

Walensky LD

doi

10.1016/j.molmed.2019.02.008

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

259-261

issue

4

eissn

1471-4914

issn

1471-499X

pii

S1471-4914(19)30043-7

journal_volume

25

pub_type

信件
  • Betulinic acid derivatives as HIV-1 antivirals.

    abstract::Betulinic acid (BA) derivatives are low molecular weight organic compounds synthesized from a plant-derived natural product. Several BA derivatives are potent and highly selective inhibitors of HIV-1. Depending on the specific side-chain modification, these compounds function by inhibiting HIV fusion or, as recently d...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2004.11.001

    authors: Aiken C,Chen CH

    更新日期:2005-01-01 00:00:00

  • Autophagy as a basis for the health-promoting effects of vitamin D.

    abstract::Autophagy is an evolutionarily conserved lysosomal self-digestion process essential for cellular homeostasis, differentiation and survival. As an adaptive response, it protects organisms against a wide range of pathologies, including cancer, infection, neurodegeneration, heart disease and ageing. Thus, compounds activ...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章

    doi:10.1016/j.molmed.2010.04.005

    authors: Høyer-Hansen M,Nordbrandt SP,Jäättelä M

    更新日期:2010-07-01 00:00:00

  • Broadly Neutralizing Antibodies against HIV: Back to Blood.

    abstract::After years of continuous exposure to HIV envelope antigens, a minority of HIV-infected individuals develop a cognate polyclonal humoral response comprising very potent and extremely cross-reactive neutralizing antibodies [broadly neutralizing antibodies (bNAbs)]. Isolated bNAbs derived from memory B cell pools have b...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2019.01.007

    authors: Dashti A,DeVico AL,Lewis GK,Sajadi MM

    更新日期:2019-03-01 00:00:00

  • Interferon gene regulation: not all roads lead to Tolls.

    abstract::Many infectious agents elicit a type I interferon response but, until recently, the molecular details that coordinate interferon (IFN)-alpha and -beta expression during infection were unknown. Innate immune pattern recognition receptors, including Toll-like receptors and cytoplasmic RNA helicases such as retinoic acid...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2005.07.006

    authors: Jefferies CA,Fitzgerald KA

    更新日期:2005-09-01 00:00:00

  • Senescent Cells Drive Frailty through Systemic Signals.

    abstract::Senescent cells drive ageing and the associated loss in health and lifespan. Whether this is mediated by systemic signalling remained unclear. Recently, Xu et al. [1] (Nat. Med. 2018;24:1246-1256) answered this question by injecting senescent cells into young mice and observing a long-lasting increase in frailty and m...

    journal_title:Trends in molecular medicine

    pub_type: 评论,杂志文章

    doi:10.1016/j.molmed.2018.09.003

    authors: Lehmann J,Baar MP,de Keizer PLJ

    更新日期:2018-11-01 00:00:00

  • MLL: a histone methyltransferase disrupted in leukemia.

    abstract::Rearrangements of the MLL gene, which is located at chromosome 11q23, are associated with aggressive acute leukemias in both children and adults. MLL regulates Hox gene expression through direct promoter binding and histone modification. MLL rearrangements occurring in leukemia include MLL fusion genes, partial tandem...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2004.08.005

    authors: Hess JL

    更新日期:2004-10-01 00:00:00

  • RBC NOS: regulatory mechanisms and therapeutic aspects.

    abstract::Nitric oxide (NO), one of the most important vascular signaling molecules, is primarily produced by endothelial NO synthase (eNOS). eNOS is tightly regulated by its substrate l-arginine, cofactors and diverse interacting proteins. Interestingly, an NO synthase (NOS) was described within red blood cells (RBC NOS), and ...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2008.05.002

    authors: Ozüyaman B,Grau M,Kelm M,Merx MW,Kleinbongard P

    更新日期:2008-07-01 00:00:00

  • Modeling Pancreatic Cancer through Somatic Editing with AAV.

    abstract::Genetically engineered mouse models have revolutionized the study of pancreatic cancer, but have several technical and practical limitations. A new adeno-associated virus (AAV)-driven somatic genome-editing model of pancreatic ductal adenocarcinoma reported by Ideno et al. (Lab. Invest. published online February 6, 20...

    journal_title:Trends in molecular medicine

    pub_type: 信件

    doi:10.1016/j.molmed.2019.02.012

    authors: Curiel-GarcÍa A,Olive KP

    更新日期:2019-05-01 00:00:00

  • Glutamine Skipping the Q into Mitochondria.

    abstract::Imported across the plasma membrane by SLC1A5, glutamine has emerged as a metabolic fuel that is catabolized by mitochondrial glutaminase to support tumor growth. The missing link between cytoplasmic and mitochondrial glutamine metabolism is now provided by Yoo et al., identifying the mitochondrial glutamine importer ...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章

    doi:10.1016/j.molmed.2019.11.004

    authors: Stine ZE,Dang CV

    更新日期:2020-01-01 00:00:00

  • CAR-T cells and solid tumors: tuning T cells to challenge an inveterate foe.

    abstract::Recent reports on the impressive efficacy of adoptively transferred T cells to challenge cancer in early phase clinical trials have significantly raised the profile of T cell therapy. Concomitantly, general expectations are also raised by these reports, with the natural aspiration to deliver this therapy over a wide r...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2012.04.009

    authors: Gilham DE,Debets R,Pule M,Hawkins RE,Abken H

    更新日期:2012-07-01 00:00:00

  • Natural killer and gammadelta T cells in haematological malignancies: enhancing the immune effectors.

    abstract::Human natural killer (NK) and gamma delta (gammadelta) T cells are potent effectors involved in the destruction of abnormal cells. Accumulating clinical and experimental data point towards a key role for NK cells and gammadelta T cells in the control of most, if not all, haematological malignancies. This review focuse...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2009.04.005

    authors: Rey J,Veuillen C,Vey N,Bouabdallah R,Olive D

    更新日期:2009-06-01 00:00:00

  • Molecular diagnostics: hurdles for clinical implementation.

    abstract::In the coming years, molecular diagnostics will continue to be of critical importance to public health worldwide. It will facilitate the detection and characterization of disease, as well as monitoring of the drug response, and will assist in the identification of genetic modifiers and disease susceptibility. A wide r...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章

    doi:10.1016/s1471-4914(02)02331-6

    authors: Fortina P,Surrey S,Kricka LJ

    更新日期:2002-06-01 00:00:00

  • Sphingosine Kinase 1: A Potential Therapeutic Target in Pulmonary Arterial Hypertension?

    abstract::Sphingosine kinase 1 (SphK1) knockout mice are protected against pulmonary hypertension and expression levels of the enzyme are increased in the lungs of pulmonary arterial hypertensive (PAH) patients. Moreover, sphingosine 1-phosphate can promote vascular remodeling/vasoconstriction in rodent and human pulmonary arte...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2017.07.001

    authors: Pyne NJ,Pyne S

    更新日期:2017-09-01 00:00:00

  • Cannabinoids and brain injury: therapeutic implications.

    abstract::Mounting in vitro and in vivo data suggest that the endocannabinoids anandamide and 2-arachidonoyl glycerol, as well as some plant and synthetic cannabinoids, have neuroprotective effects following brain injury. Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission and reduce the production of tumo...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章

    doi:10.1016/s1471-4914(02)02276-1

    authors: Mechoulam R,Panikashvili D,Shohami E

    更新日期:2002-02-01 00:00:00

  • Hedgehog checkpoints in medulloblastoma: the chromosome 17p deletion paradigm.

    abstract::Medulloblastomas often activate Hedgehog signaling inappropriately. The finding that mutations in components of this pathway are present only in few tumors suggests that additional genetic or epigenetic lesions can also lead to Hedgehog dysregulation. Chromosome 17p deletion, the most frequently detected genetic lesio...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2005.10.005

    authors: Ferretti E,De Smaele E,Di Marcotullio L,Screpanti I,Gulino A

    更新日期:2005-12-01 00:00:00

  • Recent advances in understanding serotonin regulation of cardiovascular function.

    abstract::Serotonin is an important neurohormonal factor that has been implicated in cardiovascular function. It can regulate vascular tone, act directly on cardiomyocytes and stimulate chemosensitive nerves in the heart. Cardiovascular dysfunction is observed when serotonin signaling is altered or when variation in serotonin c...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2004.03.007

    authors: Côté F,Fligny C,Fromes Y,Mallet J,Vodjdani G

    更新日期:2004-05-01 00:00:00

  • Engineering Paper-Based Sensors for Zika Virus.

    abstract::The emergence of Zika virus (ZIKV) infections in Latin America and Southeast Asia has created an urgent need for new, simple, yet sensitive, diagnostic tests. We highlight recent work using paper-based sensors coupled with CRISPR/Cas9 to detect ZIKV RNA as a new approach to achieve rapid development and deployment of ...

    journal_title:Trends in molecular medicine

    pub_type: 评论,杂志文章

    doi:10.1016/j.molmed.2016.05.009

    authors: Meagher RJ,Negrete OA,Van Rompay KK

    更新日期:2016-07-01 00:00:00

  • Vascular calcification and bone disease: the calcification paradox.

    abstract::Vascular calcification or ectopic mineralization in blood vessels is an active, cell-regulated process, increasingly recognized as a general cardiovascular risk factor. Remarkably, ectopic artery mineralization is frequently accompanied by decreased bone mineral density or disturbed bone turnover. This contradictory a...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2009.07.001

    authors: Persy V,D'Haese P

    更新日期:2009-09-01 00:00:00

  • Apoptosis-regulating proteins as targets for drug discovery.

    abstract::Defects in the regulation of apoptosis (programmed cell death) contribute to many diseases, including pathologies associated with cell loss (e.g. stroke, heart failure, neurodegeneration and AIDS), and disorders characterized by a failure to eliminate harmful cells (e.g. cancer, autoimmunity). Apoptosis is caused by a...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/s1471-4914(01)02026-3

    authors: Reed JC

    更新日期:2001-07-01 00:00:00

  • Meet Your Stress Management Professionals: The Endocannabinoids.

    abstract::The endocannabinoid signaling system (ECSS) is altered by exposure to stress and mediates and modulates the effects of stress on the brain. Considerable preclinical data support critical roles for the endocannabinoids and their target, the CB1 cannabinoid receptor, in the adaptation of the brain to repeated stress exp...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2020.07.002

    authors: deRoon-Cassini TA,Stollenwerk TM,Beatka M,Hillard CJ

    更新日期:2020-10-01 00:00:00

  • One ring to rule them all? Another cellular responsibility for PCNA.

    abstract::To prevent duplication or loss of genomic regions during DNA replication, it is essential that the entire genome is copied precisely once every S phase. Cells achieve this by mutually exclusive regulation of origin firing and licensing. A crucial protein that is involved in origin licensing is chromatin licensing and ...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章

    doi:10.1016/j.molmed.2006.08.004

    authors: Green CM

    更新日期:2006-10-01 00:00:00

  • Type 2 diabetes as a protein misfolding disease.

    abstract::Type 2 diabetes (T2D) is a highly prevalent and chronic metabolic disorder. Recent evidence suggests that formation of toxic aggregates of the islet amyloid polypeptide (IAPP) might contribute to β-cell dysfunction and disease. However, the mechanism of protein aggregation and associated toxicity remains unclear. Misf...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2015.04.005

    authors: Mukherjee A,Morales-Scheihing D,Butler PC,Soto C

    更新日期:2015-07-01 00:00:00

  • The Boosting Potential of Bacteria in Cancer Immunotherapy.

    abstract::Salmonella Typhimurium, engineered to express flagellin B, recently demonstrated unprecedented tumor control through a TLR-dependent mechanism. Here, we review new observations that support the potential of utilizing modified bacteria to enhance antitumor immunity. We also discuss the implications of these findings fo...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章

    doi:10.1016/j.molmed.2017.05.008

    authors: Binder DC,Wainwright DA

    更新日期:2017-07-01 00:00:00

  • Protein transport into the endoplasmic reticulum: mechanisms and pathologies.

    abstract::Transport into the endoplasmic reticulum (ER) is the crucial step in the biosynthesis of most secretory proteins and many membrane proteins. The products of the SIL1, SEC62 and SEC63 genes act in concert with the SEC61 complex and the molecular chaperones BiP and GRP170 to transport proteins into the ER. Interestingly...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章

    doi:10.1016/j.molmed.2006.10.004

    authors: Zimmermann R,Müller L,Wullich B

    更新日期:2006-12-01 00:00:00

  • 2-Cys peroxiredoxin function in intracellular signal transduction: therapeutic implications.

    abstract::H(2)O(2) is a reactive oxygen species that has drawn much interest because of its role as a second messenger in receptor-mediated signaling. Mammalian 2-Cys peroxiredoxins have been shown to eliminate efficiently the H(2)O(2) generated in response to receptor stimulation. 2-Cys peroxiredoxins are members of a novel pe...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2005.10.006

    authors: Kang SW,Rhee SG,Chang TS,Jeong W,Choi MH

    更新日期:2005-12-01 00:00:00

  • Huntington's Disease: Les Jeux Sont Faits?

    abstract::In a meticulous study, Humbert, Durr, and colleagues showed evidence for aberrant neurodevelopment in both Huntington's disease (HD) and mouse models of HD. We consider the implications of prenatal pathological changes for the onset and progression of HD and their relatedness to current therapeutic plans. ...

    journal_title:Trends in molecular medicine

    pub_type: 评论,杂志文章

    doi:10.1016/j.molmed.2020.08.004

    authors: Pfister EL,Aronin N

    更新日期:2020-10-01 00:00:00

  • Hippocampal Area CA2: An Overlooked but Promising Therapeutic Target.

    abstract::While the hippocampus has long been recognized as a brain structure specialized in mapping 'space' in rodents, human studies and now recent data from rodents have shown that its function extends well beyond spatial coding. Recently, an overlooked area of the hippocampus, CA2, has emerged as a critical region for socia...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2016.06.007

    authors: Chevaleyre V,Piskorowski RA

    更新日期:2016-08-01 00:00:00

  • A Maternal Functional Module in the Mammalian Oocyte-To-Embryo Transition.

    abstract::Prior to zygotic genome activation, early mammalian development relies on maternal-effect genes to orchestrate the oocyte-to-embryo transition. Recently, a subcortical maternal complex (SCMC) was identified to be essential for mouse preimplantation development. The SCMC integrates multiple proteins encoded by maternal...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmed.2017.09.004

    authors: Lu X,Gao Z,Qin D,Li L

    更新日期:2017-11-01 00:00:00

  • Virus-induced neurobehavioral disorders: mechanisms and implications.

    abstract::One hypothesis for the etiology of neuropsychiatric disorders proposes that viral infection contributes to the induction of neuronal system dysfunction, resulting in a wide range of behavioral abnormalities. Recent research in molecular biology supports this hypothesis and refocuses on the role of viral infection in t...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章

    doi:10.1016/j.molmed.2003.12.001

    authors: Tomonaga K

    更新日期:2004-02-01 00:00:00

  • Brain iron transport and neurodegeneration.

    abstract::Despite years of investigation, it is still not known why iron levels are abnormally high in some regions of the brain in neurodegenerative disorders. Also, it is not clear whether iron accumulation in the brain is an initial event that causes neuronal death or is a consequence of the disease process. Here, we propose...

    journal_title:Trends in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1016/s1471-4914(00)01910-9

    authors: Qian ZM,Shen X

    更新日期:2001-03-01 00:00:00