NDLI: Using peptide nucleic acids as gene-expression modifiers to reduce β-amyloid levels

Content Provider	Springer Nature Link
Author	McMahon, Beth M. Stewart, Jennifer Fauq, Abdul Younkin, Steven Younkin, Linda Richelson, Elliott
Copyright Year	2002
Abstract	The deposition of amyloid β peptide (Aβ) is an early and critical aspect of Alzheimer’s disease. Aβ is formed by the cleavage of amyloid precursor protein (APP). Studies of familial forms of Alzheimer’s disease indicate that elevated secretion of Aβ, particularly Aβ$_{(1–42)}$, is likely to be an etiologic agent in the disease. Aβ$_{(1–42)}$ is known to cause fibril formation and at elevated levels increases aggregation, which can lead to neuronal death. It has, therefore, been hypothesized that if the levels of Aβ, particularly Aβ$_{(1–42)}$, could be reduced that onset of Alzheimer’s disease could be slowed or possibly prevented. We, therefore, propose using PNAs targeted to APP to decrease plasma and brain levels of Aβ$_{(1–40)}$ and Aβ$_{(1–42)}$. This research project is designed to expand upon the discovery in our laboratory that systemic administration of antisense or antigene treatments utilizing peptide nucleic acids (PNAs) can be used to target and shut down proteins. Antisense strategies are methods of specifically targeting a particular protein by inhibiting translation by complementary binding to mRNA, while antigene methods inhibit transcription by complementary binding to DNA. For experiments involving antisense strategies, there are several advantages to using PNAs as opposed to the traditional oligonucleotide approaches. We initially preformed our studies in rats and identified a PNA sequence that was able to significantly reduce the levels of Aβ$_{(1–41)}$ in rat brain compared to vehicle control rats. We have switched to mice so that we can prepare to perform our experiments in a transgenic animal model of Alzheimer’s disease. We have, however, run into several technical difficulties with using mice compared to rats. In spite of this, we have identified one PNA sequence that specifically lowers mouse brain Aβ$_{(1–40)}$ Aβ$_{(1–42)}$ by 37% and 47%, respectively.
Starting Page	71
Ending Page	76
Page Count	6
File Format	PDF
ISSN	08958696
Journal	Journal of Molecular Neuroscience
Volume Number	19
Issue Number	1-2
e-ISSN	15591166
Language	English
Publisher	Humana Press
Publisher Date	2002-01-01
Publisher Place	Totowa
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Neurosciences Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Cellular and Molecular Neuroscience

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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