Jiyan Ma on Heat shock protein 70 participates in the neuroprotective response to intracellularly expressed beta-amyloid in neurons.

COMMENT The biological consequence of intracellular accumulation of Aβ peptide has recently attracted increased attention. The Aβ42 peptide is present in brains of individuals with AD and Down’s syndrome, in APP transgenic mice, and in aging monkeys [1-6]. The ob

Mark Mattson on A Little BDNF May Help Your Canary Sing

COMMENT The discoveries that neurons that mediate birdsong in canaries are replaced by new neurons produced from stem cells, and that this turnover of the neurons is regulated by testosterone in a seasonal manner, have provided important insight into the control

Nikolay Dokholyan on Exploring amyloid formation by a de novo design.

COMMENT Comment by B. Edward Bondo and Nikolay V. Dokholyan Kammerer et al. have developed a simplified

Sagar Khare on Tissue damage in the amyloidoses: Transthyretin monomers and nonnative oligomers are the major cytotoxic species in tissue culture.

COMMENT Reixach et al. study the aggregation and cytotoxicity of mutant and wild-type (WT) forms of Transthyretin (TTR), one of the 23 known human proteins involved in sporadic and familial amyloidoses. It was previously found by Kelly and coworkers that aggregat

Jie Shen on Better Model Links Polyglutamine Disease to Growth Factor VEGF

COMMENT This is an interesting paper in that it connects CBP and androgen receptor to the expression of VEGF. (Evidence that CBP regulates VEGF expression and for the connection between CBP and androgen receptor already existed.) It is curious that the authors fo

Diana Dominguez on Follow the Leader to Higher BACE Levels

COMMENT Transcriptional regulation is probably the major mode of regulating eukaryotic gene expression; however, post-transcriptional mechanisms also contribute, in many instances, to determine the final amount of a gene product that is present in the cell at a g

Daniele Zacchetti on Differential utilization of upstream AUGs in the beta-secretase mRNA suggests that a shunting mechanism regulates translation.

COMMENT The Rogers et al. paper (contributed by G.M. Edelman to PNAS) describes a possible mechanism of translational control in rat BACE-1 transcript. We have a paper in press in NAR (submitted September 25th 2003 and accepted March 2nd 2004) dealing with the sa

Gerard Drewes on MARK Homologue Sparks Tau Terror in Fruit Fly

COMMENT This paper describes an intriguing Drosophila model of tau phosphorylation causing tau neurotoxicity. So far, therapeutic approaches to tau pathology in AD did not progress beyond the preclinical stage and were mainly directed at the inhibition of the CDK

Michael Irizarry on Follow the Leader to Higher BACE Levels

COMMENT Elevated BACE at the mRNA, protein, and/or activity levels have been found in the Alzheimer's disease (AD) and aging brain. Clarifying the mechanism of BACE alterations in AD will contribute to identifying therapeutic targets. This rigorous study fur

Timothy Tiedemann on Fats, Aβ, Oxidative Stress: Feeding Forward and Backward, Killing Neurons?

COMMENT Acetyl-L-Carnitine has shown some efficacy in treating early onset AD in some small, short term trials on several parameters of memory and in one as an adjuvant therapy in combination with acetylcholinesterase inhibitors. timothytn6 0 Effects of acetyl-L-

Gunnar Gouras on Heat shock protein 70 participates in the neuroprotective response to intracellularly expressed beta-amyloid in neurons.

COMMENT Jin et al. in the American Journal of Pathology and Magrané et al. in J Neuroscience provide further support for a critical role of intraneuronal β-amyloid accumulation. Jin et al. provide compelling data indicating that in cultured neurons with chemicall

Alexei Koudinov on Fats, Aβ, Oxidative Stress: Feeding Forward and Backward, Killing Neurons?

COMMENT article, news summary, and the responses by knowledgeable commentators. Preliminary and related findings

Yusuf Hannun on Fats, Aβ, Oxidative Stress: Feeding Forward and Backward, Killing Neurons?

COMMENT The study by Cutler et al. reports on increases in the levels of the lipids ceramide and cholesterol in the aging brain. These changes are further exacerbated in Alzheimer’s disease (AD) brains, which also show decreased levels of sphingomyelin (a precurs

Kazuhiro Honda on Radical Development: Reactive Oxygen Species Critical in Development

COMMENT Is Redox Regulation of Development in Caenorhabditis elegans a Critical Issue? Shibata and colleagues (2003) present compelling evidence of reactive oxygen species (ROS) and oxidation of lipoprotein as important mediators of signal transduction. They expl

Chris Link on Heat shock protein 70 participates in the neuroprotective response to intracellularly expressed beta-amyloid in neurons.

COMMENT This is an excellent paper that describes a novel model for assaying the effects of intracellular β amyloid peptide (Aβ) in primary neurons. The motivation for these studies is the increasing realization that Aβ can accumulate intracellularly, and this in