Hydroxamic Acids

Publication Title: 
European journal of human genetics: EJHG

Spinal muscular atrophy (SMA) is the leading genetic cause of early childhood death worldwide and no therapy is available today. Many drugs, especially histone deacetylase inhibitors (HDACi), increase SMN levels. As all HDACi tested so far only mildly ameliorate the SMA phenotype or are unsuitable for use in humans, there is still need to identify more potent drugs. Here, we assessed the therapeutic power of the pan-HDACi JNJ-26481585 for SMA, which is currently used in various clinical cancer trials.

Schreml, Julia
Riessland, Markus
Paterno, Mario
Garbes, Lutz
Roflbach, Kristina
Ackermann, Bastian
Kr‰mer, Jan
Somers, Eilidh
Parson, Simon H.
Heller, Raoul
Berkessel, Albrecht
Sterner-Kock, Anja
Wirth, Brunhilde
Publication Title: 
Neurobiology of Aging

A number of neurological diseases are caused by mutations of RNA metabolism-related genes. A complicating issue is that whether under- or overfunction of such genes is responsible for the phenotype. Polyglutamine tract binding protein-1, a causative gene for X-linked mental retardation, is also involved in RNA metabolism, and both mutation and duplication of the gene were reported in human patients. In this study, we first report a novel phenotype of dPQBP1 (drosophila homolog of Polyglutamine tract binding protein-1)-mutant flies, lifespan shortening.

Tamura, Takuya
Sone, Masaki
Nakamura, Yoko
Shimamura, Teppei
Imoto, Seiya
Miyano, Satoru
Okazawa, Hitoshi
Publication Title: 
Experimental Gerontology

We tested the effects of a Class I histone deacetylase inhibitor (HDAcI), sodium butyrate (NaBu), on the longevity of normal- and long-lived strains of Drosophila melanogaster. This HDAcI has mixed effects in the normal-lived Ra strain as it decreases mortality rates and increases longevity when administered in the transition or senescent spans, but decreases longevity when administered over the health span only or over the entire adult lifespan. Mostly deleterious effects are noted when administered by either method to the long-lived La strain.

McDonald, Philip
Maizi, Brian M.
Arking, Robert
Publication Title: 
Nucleic Acids Research

Reln mRNA and protein levels are reduced by approximately 50% in various cortical structures of post-mortem brain from patients diagnosed with schizophrenia or bipolar illness with psychosis. To study mechanisms responsible for this down-regulation, we have analyzed the promoter of the human reelin gene. We show that the reelin promoter directs expression of a reporter construct in multiple human cell types: neuroblastoma cells (SHSY5Y), neuronal precursor cells (NT2), differentiated neurons (hNT) and hepatoma cells (HepG2).

Chen, Ying
Sharma, Rajiv P.
Costa, Robert H.
Costa, Erminio
Grayson, Dennis R.
Publication Title: 
The Journal of Biological Chemistry

Estrogen receptors (ER alpha/ER beta) are expressed in neuronal cells and exhibit a variety of activities in the central nervous system. ER activity is regulated in a ligand-dependent manner and by co-regulatory factors. Caveolin-1 is a recently identified co-activator of ER alpha mediating the ligand-independent activation of this steroid receptor. Here the influence of ERs on caveolin expression in human neuroblastoma SK-N-MC cells as well as in rodent brain was investigated.

Zschocke, J¸rgen
Manthey, Dieter
Bayatti, Nadhim
van der Burg, Bart
Goodenough, Sharon
Behl, Christian
Publication Title: 
Nihon Arukoru Yakubutsu Igakkai Zasshi = Japanese Journal of Alcohol Studies & Drug Dependence

Ethanol is a deleterious agent that causes various kinds of neuronal damage to both the developing and adult brain. Recent research on alcoholism implicates impaired function of neural stem cell (NSC) in the pathogenesis of ethanol-induced brain dysfunction. We previously reported that the differentiation of NSCs into neurons was significantly influenced by ethanol.

Ishii, Takao
Hashimoto, Eri
Ukai, Wataru
Tateno, Masaru
Yoshinaga, Toshihiro
Ono, Takahumi
Watanabe, Kimihiko
Saito, Satoshi
Saito, Toshikazu
Publication Title: 
Journal of Psychiatric Research

OBJECTIVE: The emerging field of psychiatric epigenetics is constrained by the dearth of research methods feasible in living patients. With this focus, we report on two separate approaches, one in vitro and one in vivo, developed in our laboratory. METHOD: In the first approach, we isolated lymphocytes from 12 subjects and cultured their cells with either 0.7 mM valproic acid (VPA), 100 nM Trichostatin A (TSA), or DMSO (control) for 24h based upon previous dose response experiments.

Gavin, David P.
Kartan, Saritha
Chase, Kayla
Jayaraman, Sundararajan
Sharma, Rajiv P.
Publication Title: 
Nature Neuroscience

Histone deacetylases (HDACs) compact chromatin structure and repress gene transcription. In schizophrenia, clinical studies demonstrate that HDAC inhibitors are efficacious when given in combination with atypical antipsychotics. However, the molecular mechanism that integrates a better response to antipsychotics with changes in chromatin structure remains unknown.

Kurita, Mitsumasa
Holloway, Terrell
GarcÌa-Bea, Aintzane
Kozlenkov, Alexey
Friedman, Allyson K.
Moreno, JosÈ L.
Heshmati, Mitra
Golden, Sam A.
Kennedy, Pamela J.
Takahashi, Nagahide
Dietz, David M.
Mocci, Giuseppe
Gabilondo, Ane M.
Hanks, James
Umali, Adrienne
Callado, Luis F.
Gallitano, Amelia L.
Neve, Rachael L.
Shen, Li
Buxbaum, Joseph D.
Han, Ming-Hu
Nestler, Eric J.
Meana, J. Javier
Russo, Scott J.
Gonz·lez-Maeso, Javier
Publication Title: 
Journal of Pharmacological Sciences

The ability to resist stress is an important defensive function of a living body. Thus, elucidation of the mechanisms by which the brain resists stress could help to pave the way for new therapeutic strategies for stress-related psychiatric disorders including depression. The present review focuses on the roles of brain 5-HT1A receptor-mediated epigenetic mechanisms in the development of resistance to emotional stress.

Tsuji, Minoru
Miyagawa, Kazuya
Takeda, Hiroshi
Publication Title: 
Antimicrobial Agents and Chemotherapy

Most current antimalarials for treatment of clinical Plasmodium falciparum malaria fall into two broad drug families and target the food vacuole of the trophozoite stage. No antimalarials have been shown to target the brief extracellular merozoite form of blood-stage malaria. We studied a panel of 12 drugs, 10 of which have been used extensively clinically, for their invasion, schizont rupture, and growth-inhibitory activity using high-throughput flow cytometry and new approaches for the study of merozoite invasion and early intraerythrocytic development.

Wilson, Danny W.
Langer, Christine
Goodman, Christopher D.
McFadden, Geoffrey I.
Beeson, James G.


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