Next-generation CRISPR gene editing tools in the precision treatment of Alzheimer's and Parkinson's disease.

Emerging gene-editing technologies, such as the CRISPR system, represent a potential pathway for precision medicine targeting the genetic and molecular causes of diseases. Second-generation CRISPR technologies, including base editing, prime editing, and engineered Cas variants, have improved fidelity and offer alternative strategies for precise gene correction, transcriptional repression or activation, and modulation of pathological pathways in neurodegeneration. These tools can correct single-nucleotide mutations, reduce pathological protein accumulation, and modulate neuroinflammatory responses, all integral to the pathogenesis of Alzheimer's disease (AD) and Parkinson's disease (PD), both chronic, progressive neurodegenerative disorders. Unfortunately, currently available treatments are limited and primarily palliative. Preclinical studies have shown promising results, with improvements in cognitive and motor deficits in animal models. However, significant challenges must be addressed to ensure safe and effective delivery to the CNS, minimize off-target effects, and address ethical concerns. Current clinical investigations aim to translate these findings into available therapeutic options. This review also identifies the biological mechanisms, therapeutic use cases, and current limitations of next-generation CRISPR systems as tools in the context of AD and PD, providing both therapeutic and research capabilities through their unique strengths. Ultimately, the future of transactional neurogenomics will determine the clinical possibilities of CRISPR-based strategies for advancing neurodegenerative disease management beyond palliative and symptomatic treatment, toward a feasible mechanistic form of disease modification.