Inez Vincent on Ectopic cell cycle events link human Alzheimer's disease and amyloid precursor protein transgenic mouse models.

COMMENT In the last few years, Karl Herrup's group has steadfastly and beautifully expounded on the involvement of cell cycle events in Alzheimer disease pathology. Their most recent paper describing cell cycle changes in APP transgenic models further nails ...

Inez Vincent on Inflammation Boosts Brain CDK5 Activity, Tau Phosphorylation

COMMENT Elevated p25 is thought to account for increased or pathological CDK5 activation that seems to be a commonality in several human neurodegenerative diseases. However, it is not yet understood how so many different etiologies lead to this common step in ...

Inez Vincent on Protein kinase CK2 is an inhibitor of the neuronal Cdk5 kinase.

COMMENT This is a beautifully done study and is timely. It will and should shift the focus in the field of Cdk5 biology to regulation of Cdk5 activity beyond p35 and p25. It also emphasizes the importance of cross-talk between Cdk5 and other protein kinases in ...

Inez Vincent on Caught in the Act: NPC1 Found to Bind Cholesterol

COMMENT Because of the accumulation of cholesterol in NPC patients having mutated NPC1, it has been assumed for many years that NPC1 is a cholesterol transporter. For the first time, the work of Ohgami et al. demonstrates a direct interaction between a ...

Inez Vincent on Herpes and AD—Virus Hitches Ride with APP

COMMENT The presence of HSV in brain has been correlated previously with Alzheimer's disease (Itzhaki and Dobson, 2002). The paper by Satpute-Krishnan et al. provides a clue for understanding this relationship in the form of a molecular interaction between ...

Inez Vincent on Amyloid deposition in APP23 mice is associated with the expression of cyclins in astrocytes but not in neurons.

COMMENT I am submitting this invited comment with the caveat that I have not had an opportunity to read the full text of this article. With that caveat in mind, it seems to me that this study is the in vivo correlate of the work published by McPhie and colleagues ...

Inez Vincent on Linking APP with Cell Cycle Reentry and Apoptosis—One Kinase Does the Trick

COMMENT McPhie et al. have done a beautiful job unraveling the signaling pathway linking FAD mutants of APP and neuronal apoptosis. Their evidence that reentry into the cell cycle is an obligatory step in this APP-induced apoptotic cascade is compelling. I'm ...

Inez Vincent on Lithium Hinders Aβ Generation, Buffing Up GSK as Drug Target

COMMENT I have never understood why GSK3α was neglected in studies of Alzheimer's neurodegeneration for the past two decades. The enzyme has over 90 percent homology with GSK3β, is also inhibited by lithium, and both isoforms are abundant in brain. The ...

Inez Vincent on Cyclin-dependent kinase activity is required for apoptotic death but not inclusion formation in cortical neurons after proteasomal inhibition.

COMMENT This is an excellent study that delineates the precise role of cdks in neuronal death using a combination of pharmacological and molecular tools. It is particularly interesting that both the proteasome and cdks are obligatory mediators of apoptosis, but ...

Inez Vincent on Cell cycle regulators in the neuronal death pathway of amyotrophic lateral sclerosis caused by mutant superoxide dismutase 1.

COMMENT This is a very interesting finding, and complements nicely the paper by Rideout et al., 2003. Our lab has also found (unpublished observations) activated cdk4 in the Nieman-Pick type C mouse model, which has an axonopathy resembling that of ALS. I find it ...

Inez Vincent on AD Cell Cycle Reentry—Early Rather Than Late

COMMENT This paper stands apart from amongst the swath of papers that describe changes in AD brain as a means of delineating the progressive neurodegenerative mechanism operating in the disease. It is a beautiful example of how a fairly simple and straightforward ...

Inez Vincent on Barriers to remember: brain-targeting chemical delivery systems and Alzheimer's disease.

COMMENT This sounds fascinating! I can't wait to learn more about CDSs, and perhaps experiment with them! ivincent 0 ...

Inez Vincent on Stress-induced hyperphosphorylation of tau in the mouse brain.

COMMENT The abstract for this paper does not adequately describe the findings of this work or their implications. I recommend reading the full paper. Essentially, the work suggests that tau hyperphosphorylation is not the work of a single protein kinase or ...

Inez Vincent on Stabilization of the cyclin-dependent kinase 5 activator, p35, by paclitaxel decreases beta-amyloid toxicity in cortical neurons.

COMMENT The conversion of p35 to p25 has been implicated as the underlying cause of cdk5 hyperactivation in many neurodegenerative conditions. The mechanism governing formation of p25 needs to be elucidated, and the present paper provides one such clue in the ...

Inez Vincent on Pin1: a therapeutic target in Alzheimer neurodegeneration.

COMMENT This work is a nice adjunct to the Bioessays review by Lu et al (Feb 2003). Animal models of altered pin1 levels/function are essential for assessing the role of pin1 in neurodegeneration, and its potenital as a therapeutic target. ivincent 0 Proline ...