Therapeutic potential of genome editing tools in neurodegenerative diseases

Progressive functional impairment of certain populations of neurons is a hallmark of neurodegenerative diseases (NDs) like Parkinson’s disease, Alzheimer’s disease, frontotemporal dementia, tauopathies, and amyotrophic lateral sclerosis. The most prominent cytological feature of degenerating neurons is pathogenic aggregates of misfolded proteins in the cytoplasm, which hamper the proper development and functioning of neuronal cells. Different approaches have been implemented to study the mechanism of pathogenesis and explore the therapeutics of different NDs. Genome editing tools are the most powerful and widely used approach to studying NDs by inducing desired modifications at the targeted genome site, offering a more promising approach to treatment than conventional techniques. This chapter covers the recent developments in the three main genome editing techniques, including transcription activator-like effector nucleases (TALENs), zinc-finger nucleases (ZFNs), and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). Despite the potential benefits of these editing tools, challenges like selecting the most suitable delivery techniques, safety issues, off-target impacts, and enhanced mosaicism must be addressed to maximize their potential in treating NDs.