Roles of Non-Coding RNA in Alzheimer's Disease Pathophysiology

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is accompanied by deficits in memory and cognitive functions. The disease is pathologically characterised by the accumulation and aggregation of an extracellular peptide referred to as amyloid-& beta; (A & beta;) in the form of amyloid plaques and the intracellular aggregation of a hyperphosphorelated protein tau in the form of neurofibrillary tangles (NFTs) that cause neuroinflammation, synaptic dysfunction, and oxidative stress. The search for pathomechanisms leading to disease onset and progression has identified many key players that include genetic, epigenetic, behavioural, and environmental factors, which lend support to the fact that this is a multi-faceted disease where failure in various systems contributes to disease onset and progression. Although the vast majority of individuals present with the sporadic (non-genetic) form of the disease, dysfunctions in numerous protein-coding and non-coding genes have been implicated in mechanisms contributing to the disease. Recent studies have provided strong evidence for the association of non-coding RNAs (ncRNAs) with AD. In this review, we highlight the current findings on changes observed in circular RNA (circRNA), microRNA (miRNA), short interfering RNA (siRNA), piwi-interacting RNA (piRNA), and long non-coding RNA (lncRNA) in AD. Variations in these ncRNAs could potentially serve as biomarkers or therapeutic targets for the diagnosis and treatment of Alzheimer's disease. We also discuss the results of studies that have targeted these ncRNAs in cellular and animal models of AD with a view for translating these findings into therapies for Alzheimer's disease.

Automated summary

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by memory and cognitive deficits, amyloid plaques, and neurofibrillary tangles. Various factors contribute to its onset and progression, and dysfunctions in both coding and non-coding genes have been implicated. Recent studies highlight the role of non-coding RNAs (ncRNAs) such as circRNA, miRNA, siRNA, piRNA, and lncRNA in AD, which could serve as potential biomarkers or therapeutic targets. Targeting these ncRNAs in cellular and animal models shows promising results for future AD therapies.