Two decades after antisense oligonucleotides (ASOs) were initially identified as agents capable of modulating RNA processing and protein expression, the first antisense oligonucleotide (ASO . Several potential therapeutic targets and strategies were tested for AD, in over 2000 clinical trials, but no disease-modifying therapy exists. In 2016, two ASOs were approved for treatment EMBO J. A is produced by the cleavage of amyloid precursor protein by Introduction Amyloid beta (A )-42 peptide elevation in the brain is one of the pathological hallmarks of Alzheimer's disease (AD) [1-3]. 528 Index Alternative splicing disease causing 446 global strategies 94-95 levels and ratios in 451-452 mechanism of 19-20 Altritol nucleic acid (ANA), (Fig. 3 Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093, Warsaw, Poland. 818 Universittsklinikum Ulm Antisense-Oligonukleotide II Therapeutisches Potenzial bei neuropsychiatrischen Erkrankungen sowie ethische und gesundheitspolitische Aspekte H. Graf 1, D. Lehmann 1,2, A. Antisense oligonucleotides - Alzheimer disease - psychiatric disorders # Interessenkonflikt. It has been hypothesized that the reduction of MAPT would result in depolymerizing neurofibrillary tangles and could be a potential strategy for the treatment of Alzheimer's disease and other tauopathies. Keywords: chemically-modied oligonucleotides; antisense oligonucleotides; Alzheimer's disease 1. Heiko Graf: keine Interessenkonflikte. PMID: 34773891. The hyperphosphorylation of the microtubule-associated protein tau (MAPT) has been implicated in various neurological diseases, including Alzheimer's disease. Evie Lewis with her parents, Elliot and . Alzheimer's disease (AD) represents a particular therapeutic challenge because its aetiology is very complex, with dynamic progression from preclinical to clinical stages. 1985;4:2757-2763. Electronic address: u.wojda@nencki.edu.pl. 1. Masters CL, Multhaup G, Simms G, et al. Amyloid beta-peptide is produced by the cleavage of amyloid precursor protein by two secretases, a β-secretase, beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and a γ-secretase. It has been hypothesised that partial inhibition of BACE1 in individuals with a high risk of developing Alzheimer’s disease may be beneficial in preventing cognitive decline. The maximal length of ASOs was defined as under 30 nucleotides because longer ASOs proved to be unstable in vivo.Then followed ribozymes and DNA-zymes, RNA or DNA ASOs with intrinsic nuclease activity intended for direct cleavage of a target mRNA [13,14] (Fig. Amyloid beta (A)-42 peptide elevation in the brain is one of the pathological hallmarks of Alzheimer's disease (AD) [1,2,3].A is produced by the cleavage of amyloid precursor protein by two secretases, a -secretase, beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and a -secretase [].Since the amyloid precursor protein is cleaved first by BACE1, a rate . [ PMC free article] [ PubMed] [ Google Scholar] 19. This failure indicates that AD, as a multifactorial disease, may require multi . Introduction. Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. Review Antisense oligonucleotides for Alzheimer's disease therapy: from the mRNA to miRNA paradigm Wioleta Grabowska-Pyrzewicza, Andrew Wanta, Jerzy Leszekb, Urszula Wojdaa,* a Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093, Warsaw, Poland b Department of Psychiatry, Wroclaw Medical University . Claudia Diana Wurster: Beraterttigkeit fr die Firma Hoffmann-La Roche; Honorarvortrge fr die Firma Biogen sowie Teilnahme an einem AdBoard Meeting der Firma Biogen . 2c).A proof of concept was also obtained for RNA ASOs which were designed either to decrease mRNA translation by means of a . PMCID: PMC8602003. This work aimed to collect from the existing literature examples of inverse comorbidity in which ncRNAs seem to play a key role, and investigated the example of mir-519a-3p, and one of its target genes Poly (ADP-ribose) polymerase 1, for the inverse comorosity mechanism between some cancers and PD. In this . Antisense oligonucleotides, Alzheimer dis-ease, psychiatric disorders Summary Antisense oligonucleotides (ASO) are single-stranded nucleic acids strings that bind to a complementary sequence of the pre-mRNA or mRNA, modulate transcription and/or translation and thus, protein expression. 2b). 2 Department of Psychiatry, Wroclaw Medical University, Wybrzee Pasteura 10, 50-367 Wroclaw, Poland. A class of drugs that silence the effects of faulty genes could help tackle brain diseases but a halted clinical trial has brought the field up short. Amyloid beta (A)-42 peptide elevation in the brain is one of the pathological hallmarks of Alzheimer's disease (AD) [1,2,3].A is produced by the cleavage of amyloid precursor protein by two secretases, a -secretase, beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and a -secretase [].Since the amyloid precursor protein is cleaved first by BACE1, a rate-limiting step . Diana Lehmann: keine Interessenkonflikte.