Dose-Response Relationship, Drug

Publication Title: 
Aging Cell

This past decade has seen the identification of numerous conserved genes that extend lifespan in diverse species, yet the number of compounds that extend lifespan is relatively small. A class of compounds called STACs, which were identified as activators of Sir2/SIRT1 NAD+-dependent deacetylases, extend the lifespans of multiple species in a Sir2-dependent manner and can delay the onset of age-related diseases such as cancer, diabetes and neurodegeneration in model organisms.

Author(s): 
Yang, Hongying
Baur, Joseph A.
Chen, Allen
Miller, Christine
Adams, Jeffrey K.
Kisielewski, Anne
Howitz, Konrad T.
Zipkin, Robert E.
Sinclair, David A.
Publication Title: 
CNS neuroscience & therapeutics

Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative disease of adults which preferentially attacks the neuromotor system. Riluzole has been used as the only approved treatment for amyotrophic lateral sclerosis since 1995, but its mechanism(s) of action in slowing the progression of this disease remain obscure. Searching PubMed for "riluzole" found 705 articles published between January 1996 and June 2009.

Author(s): 
Bellingham, Mark C.
Publication Title: 
Biogerontology

2-Deoxy-D-glucose (2-DG) and dehydroepiandrosterone (DHEA) have been hypothesized to extend lifespan via mimicking calorie restriction (CR). Activation of sirtuins has been proposed to contribute to life extension of CR by increasing intercellular levels of NAD(+) in several organisms. However, it is unclear whether 2-DG and DHEA may affect intracellular NAD(+) levels and human sirtuin 1 (SIRT1) activities. Here, using human fibroblast Hs68 cells we showed that 2-DG increased intracellular NAD(+) levels in both time- and concentration-dependent manners.

Author(s): 
Yang, Nae-Cherng
Song, Tuzz-Ying
Chen, Mei-Yau
Hu, Miao-Lin
Publication Title: 
Experimental Gerontology

The field of toxicology adopted the threshold dose response in the early decades of the 20th century. The model was rapidly incorporated into governmental regulatory assessment procedures and became a central feature of chemical evaluation and assessment. The toxicological community never validated the capacity of this model to make accurate predictions throughout the remainder of the 20th century. A series of recent investigations have demonstrated that the threshold and linear dose response model failed to make accurate predictions in the low dose zone.

Author(s): 
Calabrese, Edward J.
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.

Author(s): 
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: 
Expert Opinion on Drug Discovery

INTRODUCTION: Mild stress-induced hormesis is becoming increasingly attractive as an ageing interventional strategy and is leading to the discovery of hormesis-inducing compounds called hormetins.

Author(s): 
Rattan, Suresh I. S.
Publication Title: 
European Cells & Materials

Covalent modifications of titanium with small molecules known to promote human osteoblast maturation are especially attractive in developing superior biomaterials. An important step in securing competent bone formation at implant sites is promoting the formation of mature osteoblasts, either from committed pre-osteoblasts or from their mesenchymal progenitors.

Author(s): 
Mansell, Jason P.
Brown, Judith
Knapp, Jonathan G.
Faul, Charl F. J.
Blom, Ashley W.
Publication Title: 
Human & Experimental Toxicology
Author(s): 
Boxenbaum, H.
Publication Title: 
Human & Experimental Toxicology
Author(s): 
Neafsey, P. J.
Publication Title: 
Human & Experimental Toxicology
Author(s): 
Stevenson, D. E.
Sielken, R. L.

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