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Antisense oligonucleotides for Alzheimer's disease therapy: from the mRNA to miRNA paradigm
- Source :
- EBioMedicine, EBioMedicine, Vol 74, Iss, Pp 103691-(2021)
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- Alzheimer's disease (AD) represents a particular therapeutic challenge because its aetiology is very complex, with dynamic progression from preclinical to clinical stages. Several potential therapeutic targets and strategies were tested for AD, in over 2000 clinical trials, but no disease-modifying therapy exists. This failure indicates that AD, as a multifactorial disease, may require multi-targeted approaches and the delivery of therapeutic molecules to the right place and at the right disease stage. Opportunities to meet the challenges of AD therapy appear to come from recent progress in knowledge and methodological advances in the design, synthesis, and targeting of brain mRNA and microRNA with synthetic antisense oligonucleotides (ASOs). Several types of ASOs allow the utilisation of different mechanisms of posttranscriptional regulation and offer enhanced effects over alternative therapeutics. This article reviews ASO-based approaches and targets in preclinical and clinical trials for AD, and presents the future perspective on ASO therapies for AD.<br />Graphical abstract Image, graphical abstract
- Subjects :
- antisense oligonucleotide
Medicine (General)
Amyloid beta
Genetic enhancement
RNA therapy
RNA delivery
Disease
Review
Bioinformatics
General Biochemistry, Genetics and Molecular Biology
ASO, Antisense oligonucleotide
R5-920
Alzheimer Disease
microRNA
medicine
Aβ, Amyloid beta
Humans
Gene Regulatory Networks
Molecular Targeted Therapy
RNA, Messenger
Neurodegeneration
miRNA
Brain Chemistry
Messenger RNA
therapy
clinical trials
CSF, Cerebrospinal fluid
biology
business.industry
Neurofibrillary tangle
General Medicine
Alzheimer's disease
Oligonucleotides, Antisense
medicine.disease
BBB, Blood-brain barrier
gene therapy
Clinical trial
MicroRNAs
Gene Expression Regulation
NFT, Neurofibrillary tangle
biology.protein
Medicine
AD, Alzheimer's disease
business
preclinical testing
APP, Amyloid precursor protein
Subjects
Details
- Language :
- English
- ISSN :
- 23523964
- Volume :
- 74
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....d29cce4e1140f2066726bcb229d5e3c7