Review on STRs in neurodegeneration, their understudy in Alzheimer’s, and potential for disease discovery. - tlooto, The Most Powerful AcademicGPT

Short tandem repeats (STRs), repetitive DNA motifs of 2–6 base pairs, are pervasive and dynamic components of the human genome. Once dismissed as “junk DNA,” STRs have now been recognized as key drivers of genetic diversity, gene regulation, and contributors to both monogenic and complex diseases, especially within the nervous system[1][2][3]. STR instability—mediated mainly by DNA replication slippage—results in highly polymorphic regions that influence regulatory sequences, coding regions, and intergenic DNA, with profound functional and pathological consequences. a) STRs in Neurodegenerative Diseases The pathogenic expansion of STRs stands among the best-documented genetic mechanisms for a range of neurodegenerative disorders, notably Huntington’s disease (CAG repeats), fragile X syndrome (CGG), some forms of ataxia, and amyotrophic lateral sclerosis/frontotemporal dementia (C9orf72 GGGGCC expansions)[3][4]. Such repeat expansions often trigger toxicity through abnormal RNA, disrupt