Michael Ehlers on Ubiquitin Protease Implicated in Ataxia

COMMENT Ubiquitin and Synaptic Dysfunction: Ataxic Mice Highlight New Common Themes in Neurologic Disease The gene responsible for the neurologic symptoms in ataxia mice has been identified and shown to encode a ubiquitin-specific protease. This new study reveals

Tomiichiro Oda on Design and synthesis of dual inhibitors of acetylcholinesterase and serotonin transporter targeting potential agents for Alzheimer's disease.

COMMENT Sample of RS-1259 is available upon request. Contact T. Kaneko (tkanek@shina.sankyo.co.jp) for more information. 0 odatom

Dale Schenk on The Alzheimer's Vaccination Story, Continued

COMMENT Two recent papers on Aβ immunotherapy and Alzheimer's disease provide additional insight and both describe guarded optimism for the overall approach going forward. The paper by McLaurin et al. describes a very careful, in-depth analysis of the antibo

Craig Atwood on The Alzheimer's Vaccination Story, Continued

COMMENT have commented elsewhere (Check, 2002; Munch and Robinson, 2002a,b; Smith et al., 2002a) that

Dave Morgan on The Alzheimer's Vaccination Story, Continued

COMMENT The paper by Hock et al from the Zurich group was very informative. Perhaps most interesting was the discussion regarding the one patient who had meningitis symptoms. This patient had antibody titers in CSF that equaled those in plasma, indicating a sever

Edward Koo on Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch.

COMMENT First of a series of papers on APH-1 and gamma cleavage in mammalian cells, following the paper from Exelixis on c.elegans and flies. 0 edkoo

Edward Koo on Alzheimer's second patient: Johann F. and his family.

COMMENT The second Alzheimer patient may well be a FAD case. It represents a "plaque only" case and I wonder if it's like the "cotton wool" plaques seen in some PS1 mutation. I hope someone can sequence the gene to find out. 0 edkoo

Edward Koo on Direct visualization of the gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein: association with Fe65 and translocation to the nucleus.

COMMENT Confirmatory study but lovely pictures, nonetheless. 0 edkoo

Edward Koo on Beta-amyloid plaques in a model for sporadic Alzheimer's disease based on transgenic anti-nerve growth factor antibodies.

COMMENT First detailed characterization of the Aβ immunoreactive deposits in these anti-NGF mice. A lot of questions were raised since the initial publication in PNAS a couple of years ago. In this paper, the changes are impressive but these are really not tradit

Edward Koo on Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations.

COMMENT A potential explanation for selective vulnerability of motoneurons in ALS. Whether the motoneurons cultured from embryos can be extended to other neurons in the body is unclear. The curious sparing of oculomotor neurons remains a big mystery to me. 0 edko

Edward Koo on The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts.

COMMENT Convincing evidence that ADAM10 is requred for notch S2 cleavage but unclear how it may be involved in APP alpha secretase cleavage. Ultimately, alpha-secretase may indeed be a collection of protease rather than one, could gamma be the same?? 0 edkoo

Fred van Leeuwen on Ubiquitin Protease Implicated in Ataxia

COMMENT The USP’s belong to the family of deubiquitinating enzymes (DUB’s) that are essential for subsequent proteasomal activity. The other family members are ubiquitin C-terminal hydrolases (UCH) that have been associated with Parkinson’s disease and gracile ax

John Hardy on Amyloid-beta immunotherapy for Alzheimer's disease: the end of the beginning.

COMMENT The immunization story has really been a rollercoaster ride of excitement and then despair. This review discusses the work in a more sober light. It is too early to know whether this approach will work, but early L-dopa trials were generally a failure. 0

George Perry on Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration.

COMMENT Eat Less, Live More —But Why? Comment by George Perry and Mark A. Smith Institute of Pathology,

George Perry on The harlequin mouse mutation downregulates apoptosis-inducing factor.

COMMENT Harlequin and Alzheimer Disease: Remarkable Parallels If it takes years to die, it is not by an apoptotic mechanism. Klein and colleagues (2002) present an excellent model for this assertion and a couple of other phenomena that are present in Alzheimer di