Antisense oligonucleotides (ASOs) and CRISPR systems are promising gene therapy treatments for Alzheimer's disease
Moataz Dowaidar
Abstract
Animal models, together with the emergence of new technology, have considerably increased our understanding of the molecular processes implicated in Alzheimer's disease (AD) pathogenesis. These advancements have elucidated numerous critical A plaque development mechanisms, and it is quite some time until we can identify a viable cure for Alzheimer's disease. Animal models don't perfectly mimic the disease's intricacy. Another key challenge is the lack of molecular markers to detect early stages of the disease in the vast majority of patients. Precise and detailed diagnostic and therapeutic instruments are highly sought for. Dysregulation of AS may be present in up to 90% of all Alzheimer's cases. Using genetic polymorphisms such as sQTLs, which alter splicing processes involved in Alzheimer's disease, can help identify those who are at risk of the disease and may benefit from routine brain imaging to detect early stages of the disease.Human transcriptome and proteome complexity is impacted by AS. AS governs a distinct collection of genes than those regulated at the transcriptional level, and represents a second, adaptive layer of gene expression regulation. In fact, coordinated AS programs are important in embryonic development and extracellular signal response.The AD brain puts neurons and microglia under various stress. UPRER is triggered when one experiences dietary limitation, changes in redox potential, or if their calcium levels are too low. UPRER may both protect neurons and induce apoptosis in some instances. Furthermore, diabetes and mitochondrial dysfunction are rather prevalent, associated with elevated ROS formation (for a review on the connection between cellular stress and AD). Stress, along with the activation of the immune system, is known to have an effect on AS. The finding of stress patterns in the AD brain, which might help reduce AD risk through easy lifestyle alterations, may be attainable by transcriptome analysis.Research on the extensive inter-AS networks in AD must continue. The functional roles of several AS isoforms and their impact on AD are unknown; Splicing factors may be part of regulatory circuits that modulate the expression of other splicing factors, as previously reported; Patient-specific RBP aggregation afflicts a subset of AD patients, making identification of these patient-specific features difficult. Alzheimer's disease could be better understood and maybe new routes for the development of other neurodegenerative disorders could be discovered if characterizing splicing dysregulation is used.