New hypothesis posited for amyloid disease

[IMG]aoladp://MA16719201-0001/empty.gif[/IMG] NewsTrack - Science
Published: April 30, 2007 at 10:37 AM
http://www.upi.com/NewsTrack/Science...yloid_disease/

LOS ANGELES, April 30 (UPI) -- A U.S. study suggests degenerative diseases such as Alzheimer's, Parkinson's and type 2 diabetes might share common molecular level structural features.
The findings by David Eisenberg and colleagues at the University of California-Los Angeles suggest an atomic-level hypothesis for those conditions.
It's already known amyloid diseases share certain similarities, since in each disease a different protein folds abnormally. That yields clumps known as amyloid fibrils. But the fibril aggregates are always remarkably similar.
Eisenberg's study identified 30 short fibril-forming peptides taken from a large range of amyloid diseases and solved the atomic structure of 13 of them. The findings reveal one common feature: the "steric zipper" that "glues" together pairs of interwoven amino acids called beta-sheets.
The researchers said their study might help to explain why amyloid fibrils from different diseases are so strong, despite the fact that they are formed from different proteins. It might also lead to new therapies for the illnesses. The study is presented online in the journal Nature.

Journal of Neurochemistry [2007] Apr 16; [Epub ahead of print]
(Rite I, Machado A, Cano J, Venero JL.)

Blood-brain barrier disruption induces in vivo degeneration of nigral dopaminergic neurons.

We have evaluated the possibility that changes in the vascular system may constitute a contributing factor for the death of nigral dopaminergic neurons in Parkinson's disease.

Thus, we have employed intranigral injections of vascular endothelial growth factor (VEGF), the most potent inducer of blood-brain barrier (BBB) permeability. [The blood brain barrier, between the blood and the brain, usually protects the brain against toxicity]

A single dose of 1 mug of VEGF, chosen from a dose-response study, highly disrupted the BBB in the ventral mesencephalon in a time-dependent manner.

A strong regional correlation between BBB disruption and loss of tyrosine hydroxylase-positive neurons [the cells involved in Parkinsons' Disease] was evident.

Moreover, Fluoro-Jade B labelling showed the presence of dying neurons in the substantia nigra in response to VEGF injection. High number of TUNEL-positive nuclei was observed in this area along with activation of caspase 3 within nigral dopaminergic neurons.

Analysis of the glial population demonstrated a strong inflammatory response and activation of astroglia in response to BBB disruption.

We conclude that disruption of the BBB may be a causative factor for degeneration of nigral dopaminergic neurons.

to explain agents that will cause brain disease, be they plaques and tangles in AD or lewy bodies in PD an other diseases. Is first the structures made of b-pleated sheets can't be "unzipped" so they can be chopped up into smaller fragments that can then go BACK out across the BB-barrier.
For small molecules that are toxic, there is usually something in common. These are uncharged and lipophilic when they cross INTO the BB-Barrier, and become charged and/or lipophobic via intracranial metabolism, so that they are "stuck in the brain because they cant go back out the way they came in, and are free to do their dirty work before they can be properly conjugated and disposed of.

What?? The only thing that came to mind as I read this post was, but "Can she bake a cherry pie...?" You two are just a couple of showoffs!!

If it's my culinary talents you are calling into question, all I can say is, "why bake one when the supermarket makes them perfectly?"

geesh,

of course you are quite right. We have left those activities to fully functioning professional bakers these days. You must have been confused by my feminine pronoun I was actually talking about the two chemistry heads ....they are really quite impressive when they get on all the feathers and strut their stuff. But how are they when it comes to the simple things in life? Well boys...can either of you bake a cherry pie without going to a receipe book? Actually, I'm very glad we have that kind of brainpower here. As Ron says in another thread, we are a diverse group of immense talent (not an exact quote). I really shouldn't take shots at other people's speciality's. Hmm, but back to Cherry pie....what have I got in my cupboards that might make a suitable substitute at this late hour?

Paula,
It seems to be saying the formation of protein clumps is similar in these diseases, but to me it doesn't seem to be saying much about the BBB. However, my medical knowledge is not up to scratch.
I am glad DAffy has joined us in postng a paper with the statements,
"We conclude that disruption of the BBB may be a causative factor for degeneration of nigral dopaminergic neurons." and
"Blood-brain barrier disruption induces in vivo degeneration of nigral dopaminergic neurons."
So far I have seen nothing to refute the idea.
Ron