Potential roles of telomeres and telomerase in neurodegenerative diseases

Telomeres, essential DNA-protein complexes located at chromosome ends, play a critical role in preventing chromosome fusion, recombination, and degradation, thus ensuring genomic stability. When telomeres reach a limiting shortened length, they will activate DNA damage checkpoints, stop cell division and trigger replicative senescence. Telomerase is composed of RNA and protein, which can synthesize telomeres repeat sequences, and elongate telomeres. Studies have shown that telomere length (TL) and telomerase activity are closely involved in aging, aging-related degenerative diseases, and tumors. Neurodegenerative diseases (NDDs) are one of the major aging-related diseases caused by both genetic and environmental factors, characterized by insidious onset, difficult diagnosis, irreversible disease progression, and lack of effective treatments, which brings a heavy burden to society and families. Currently, many studies have noted variations in leukocyte telomere length (LTL) and telomerase activity in NDDs, suggesting a vital role for telomeres and telomerase in NDD pathogenesis. This review explores the relationship between TL and NDDs, examines telomerase as a potential therapeutic target, and discusses emerging biomarkers and intervention strategies for NDD diagnosis and treatment.