Aging is a prominent risk factor for many
neurodegenerative disorders, such as
Alzheimer's disease (AD).
Alzheimer's disease is characterized by progressive
cognitive decline,
memory loss, and neuropsychiatric and behavioral symptoms, accounting for most of the reported
dementia cases. This disease is now becoming a major challenge and burden on modern society, especially with the aging population. Over the last few decades, a significant understanding of the pathophysiology of AD has been gained by studying
amyloid deposition, hyperphosphorylated tau, synaptic dysfunction, oxidative stress,
calcium dysregulation, and
neuroinflammation. This review focuses on the role of non-canonical secondary structures of
DNA/RNA G-quadruplexes (G4s, G4-
DNA, and G4-
RNA), G4-binding
proteins (G4BPs), and helicases, and their roles in aging and AD. Being critically important for cellular function, G4s are involved in the regulation of
DNA and
RNA processes, such as replication, transcription, translation,
RNA localization, and degradation. Recent studies have also highlighted G4-DNA's roles in inducing
DNA double-strand breaks that cause
genomic instability and G4-RNA's participation in regulating stress granule formation. This review emphasizes the significance of G4s in aging processes and how their homeostatic imbalance may contribute to the pathophysiology of AD.