Long Noncoding RNAs in Neurodegenerative Diseases: Pathogenesis and Potential Implications as Clinical Biomarkers

Abstract

Neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), are progressive and ultimately fatal. NDD onset is influenced by several factors including heredity and environmental cues. Long noncoding RNAs (lncRNAs) are a class of noncoding RNA molecules with: (i) lengths greater than 200 nucleotides, (ii) diverse biological functions, and (iii) highly conserved structures. They directly interact with molecules such as proteins and microRNAs and subsequently regulate the expression of their targets at the genetic, transcriptional, and post-transcriptional levels. Emerging studies indicate the important roles of lncRNAs in the progression of neurological diseases including NDDs. Additionally, improvements in detection technologies have enabled quantitative lncRNA detection and application to circulating fluids in clinical settings. Here, we review current research on lncRNAs in animal models and patients with NDDs. We also discuss the potential applicability of circulating lncRNAs as biomarkers in NDD diagnostics and prognostics. In the future, a better understanding of the roles of lncRNAs in NDDs will be essential to exploit these new therapeutic targets and improve noninvasive diagnostic methods for diseases.

Nucleic acid liquid biopsies in Alzheimer's disease: current state, challenges, and opportunities

“…Additionally, another RNA-seq study in ALS also described lncRNA dysregulation, and similar implications in PD, further indicating lncRNA utility in AD and other neurodegenerative diseases [ 119 , 120 ]. LncRNAs have also been described in brain tissues as well as specific cell types in AD, further indicating their potential role as a nucleic acid in liquid biopsies in AD (Reviewed in [ 121 , 122 ]). Finally, lncRNAs are also detectable in plasma- and CSF-derived EVs, however, studies are insufficient and require further investigation (Reviewed in [ 123 ]).…”

Research Progress on the Inflammatory Effects of Long Non-coding RNA in Traumatic Brain Injury

“…Recently, it was discovered that NEAT1 levels were significantly upregulated in the peripheral blood cells of PD patient ( Boros et al, 2020 ). Amyotrophic Lateral Sclerosis (ALS) is prevalent form of motor neuron disease, Data have shown that NEAT1_2 was minimally expressed in the motor neurons of healthy people but highly expressed in the motor neurons of people with early-stage ALS, thus suggesting its utility as a biomarker for early ALS diagnostics ( Zhang M. et al, 2021 ). LncRNAs are particularly attractive biomarkers because they are stable in the blood and other biofluids, and can be readily detected in easily-obtained biofluid samples.…”

Nucleic Acid Liquid Biopsies in Alzheimer’s Disease: Current State, Challenges, and Opportunities

“…Additionally, another RNA-seq study in ALS also described lncRNA dysregulation, and similar implications in PD, further indicating lncRNA utility in AD and other neurodegenerative diseases 119,120 . LncRNAs have also been described in brain tissues as well as specific cell types in AD, further indicating its potential role as a nucleic acid in liquid biopsies in AD (Reviewed in 121,122 ). Finally, lncRNAs are also detectable in plasma-and CSF-derived EVs, however studies are insufficient and require further investigation (Reviewed in 123 ).…”