Biomedical Engineering Reference
In-Depth Information
for small molecules that block OGG1 function. This work may also be relevant to
research on other diseases, such as Alzheimer's and Parkinson's, in which oxidative
lesions are believed to play a role.
In animal models, intrastriatal grafts of fetal striatal tissue containing projection
neurons reestablish connections with the globus palidus and receive inputs from
host cerebral cortex. This level of reconstruction of corticostriatopallidal circuitry is
sufficient to reverse motor and cognitive deficits in rats and monkeys [
62
] .
Clinical trials with intrastriatal transplantation of human fetal striatal tissue sup-
port the cell replacement strategy in Huntington's disease (HD). The grafts survived
without typical pathology, contained striate projection neurons, and received affer-
ents from the patient's brain. However, the extent of clinical benefits was unclear
[
54,
55
]. One open-label trial indicated cognitive and motor improvements [
76
]
whereas outcome was unchanged in other. Clinical improvement was associated
with reduction of striatal and cortical metabolism, suggesting that the grafts had
restored function in striato-cortical neural loops. Substantial benefit following cell
therapy will require that many more grafted striatal neurons survive than the low
numbers achieved in the trials with the fetal tissue. The stem cell technology could
markedly increase the availability of such cells.
Basic research should now explore how to generate and select striatal projection
neurons from stem cells, and probably combine stem cell therapy with accommoda-
tion of oxidative damages in DNA involved in this disease.
Researchers are using the grid-computation method, sharing tasks over multi-
ple computers, in order to learn about the molecular nature of diseases that are
caused from errors in protein folding. The aim of this project is to better under-
stand protein folding, what happens when proteins do not fold correctly, and the
diseases that result from this protein misfolding (
http://www.aboutdementia.com/
articles/about-huntingtons/huntingtons-causes.php
). Once the causes of protein
misfolding are discovered, cures for diseases such as Alzheimer's disease,
Huntington's disease, cystic fibrosis, BSE, and cancers could find a cure.
Misfolding of proteins causes clumps of proteins to gather in the brain, causing
diseases. Proteins fold very quickly, some as fast as a millionth of a second. One
of the diseases, currently focusing on, is Huntington's disease. This disease results
from the aggregation of various proteins. If proteins contain long enough strands
that contain numerous repeats of the amino acid, glutamine aggregates begin to
form, causing the disease. This abnormally long of a repeated section of the amino
acid glutamine in the DNA sequence has been thought to stem from an inherited
gene and has been given the name, huntingtin gene. A healthy person has a string
of 9-39 glutamines, whereas, Huntington's patients have 36-121 glutamines
(
http://www.aboutdementia.com/articles/about-huntingtons/huntingtons-causes.
php
). This protein folding aspect is examining the structure of poly-glutamine
aggregates and is attempting to predict the pathway that forms these aggregates.
The goal of these Huntington's studies is to find drug design approaches so
Huntington's can be find a method to stop the disease from forming the aggregate
pathway. Thus, it can be used in future as a preventive, while stem cell replace-
ment therapy, as a curative approach to disease.
