Alyssa Koeter
Nucleic
Acid Aptamer Selection Against Amyloid β-peptide (1-42) for the inhibition of
Senile Plaques in Alzheimer’s Disease
Alzheimer’s is a
neurodegenerative disorder that affects 5.4 million people and is the 6th
leading cause of death in the United States alone.1 It is a form of
dementia that worsens over time until a person can no longer have a
conversation or respond to environmental stimuli.2
The major constituents of this disease are senile plaques and tangles that result in the death and damage of nerve cells through oxidative stress.3 These plaques are present in everyone, but they are more frequent in Alzheimer’s patients.2 Amyloid β-peptide makes up the majority of these plaques.3
The major constituents of this disease are senile plaques and tangles that result in the death and damage of nerve cells through oxidative stress.3 These plaques are present in everyone, but they are more frequent in Alzheimer’s patients.2 Amyloid β-peptide makes up the majority of these plaques.3
The
specific aim of my research is to inhibit Amyloid β-peptides and therefore
decrease the number of senile plaques present in Alzheimer’s patients and
lessen the oxidative stress on their brains. This will be done through
developing an aptamer that binds to and obstructs its production. Improper
folding of the Amyloid β-peptide protein results in large insoluble masses of
fragments that eventually build up into senile plaques.4 If there
are fewer proteins, the risk of improper folding lowers and plaques are not
formed. Aptamers are oligonucleic acid molecules that bind to their targets
with high affinity. They are found through in-vitro selection and can be used
therapeutically or diagnostically.
The
goal of my research is to find an aptamer that inhibits the reproduction of
Amyloid β-Peptide and formation of senile plaques. If this is achieved, the
oxidation stress on Alzheimer’s patients’ brains will be lessened and the
enzyme functions of nerve cells will remain intact. As a result, most of the
cells will remain alive, and the neurodegeneration will proceed at a normal
aging rate rather than the accelerated one of Alzheimer’s patients.
The
target, Amyloid β-Peptide (1-42) (human), is produced by R&D Systems, and
its catalog number is 1428. One hundred micrograms costs $119.00.
1 Alzheimer's
Association. 2012 “Alzheimer's disease facts and figures.” Alzheimer's and
Dementia: The
Journal of the Alzheimer's Association. March 2012; 8:131–168
2 Alzheimer's
Association. 2012. What Is Alzheimer's? Alzheimer's and Dementia: The
Journal
of the Alzheimer's
Association. March 2012; 8
3 Drake, Jennifer,
Christopher D. Link, and D. Allan Butterfield. "Oxidative Stress Precedes
Fibrillar
Deposition of Alzheimer's Disease Amyloid β-peptide (1-42) in a Transgenic
Caenorhabditis Elegans Model." Neurobiology
of Aging 24 (2003): 415-20. Elsevier, 22 Nov. 2002. Web. 3 Sept. 2012
4 Rahimi, Farid, and Gal
Bitan. "Selection of Aptamers for Amyloid β-Protein, the Causative
Agent of
Alzheimer's Disease." Journal of Visualized Experiments 39 (2010):
n. pag. NCBI. PMC, 13 May 2010. Web. 4 Sept. 2012
2 comments:
Dear Alyssa,
Here are some thoughts:
1. well, you want to select an aptamer against amyloid beta, which is a small peptide that doesn't have a tag on it (such as biotin, Fc, his, etc.). So - we can't use the filter selection method & we can't immobilize the peptide to beads. :(
I emailed R&D to see if we could have the peptide biotinylated. I think this is a long-shot, so let's come up with some back-up plans:
* look for other Alzheimer’s Disease targets that have tags and/or are big enough for filter selections (>15-18 kDa).
* we could look into other biotinyation rxns & purfication methods ... meaning we might be able to biotinylate ourselves.
2. add figure legend
3. cite the journal (never cite pubmed).
4. cite primary literature
5. specific aims should stand on their own & not be part of a paragraph.
6. please don't write in 1st person.
7. be specific - if you want to develop a therapeutic, then say you want to develop a therapeutic aptamer reagent that does this ....
8. include the cost per a round & the molecular weight of your reagent (goes at end).
9. please reconsider your figure ... cartoons are nice.
Let's talk again soon & let me know what you find as far as alternative targets.
All the best,
Gwen
antibodies and synthetic chemistry. Our extensive expertise is translated into high quality products and world-class services to ensure the maximum satisfaction of the customers. Peptide Nucleic Acid
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