Regulatory Roles of Long Non-Coding RNAs in the Central Nervous System and Associated Neurodegenerative Diseases

Abstract

Accumulating studies have revealed that the human genome encodes tens of thousands of long non-coding RNAs (lncRNAs), which participate in multiple biological networks modulating gene expression via transcriptional, post-transcriptional and epigenetic regulation. Strikingly, a large fraction of tissue-specific lncRNAs are expressed in the Central Nervous System (CNS) with precisely regulated temporal and spatial expression patterns. These brain-specific lncRNAs are also featured with the cell-type specificity, the highest signals of evolutionary conservation, and their preferential location adjacent to brain-expressed protein-coding genes. Mounting evidence has indicated dysregulation or mutations in lncRNA gene loci are associated with a variety of CNS-associated neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, Huntington’s diseases, Amyotrophic Lateral Sclerosis and others. However, how lncRNAs contribute to these disorders remains to be further explored and studied. In this review article, we systematically and comprehensively summarize the current studies of lncRNAs, demonstrate the specificity of lncRNAs expressed in the brain, their functions during neural development and expression profiles in major cell types of the CNS, highlight the regulatory mechanisms of several studied lncRNAs that may play essential roles in the pathophysiology of neurodegenerative diseases, and discuss the current challenges and future perspectives of lncRNA studies involved in neurodegenerative and other diseases.

Identification of Novel LncRNA Biomarkers and Construction of LncRNA-Related Networks in Han Chinese Patients with Ischemic Stroke

“…Circulating lncRNAs are a novel category of promising biomarkers and play key roles in screening, diagnosis, process, treatment, and prognosis of many diseases [17][18][19]. Serum lncRNA-RP11-445H22.4 has been confirmed as a biomarker for detecting breast cancer and exhibited AUC of 0.904 (Sp = 74%, Se = 92%) [20].…”

The role of LINC00094/miR‐224‐5p (miR‐497‐5p)/Endophilin‐1 axis in Memantine mediated protective effects on blood‐brain barrier in AD microenvironment

“…34,35 TJs are comprised of the ZOs, occludin as well as claudins, which are considered the basic components responsible for proper function and integrity of BBB. 38 It is urgent to ascertain the dysregulated lncRNAs and the underlying mechanism in a variety of neurodegenerative disorders. 38 It is urgent to ascertain the dysregulated lncRNAs and the underlying mechanism in a variety of neurodegenerative disorders.…”

No Evidence for Recent Selection at FOXP2 among Diverse Human Populations

“…Mechanistically, lncRNAs have been shown to impact chromatin states through cis- and trans-acting mechanisms, thereby functioning to fine-tune gene expression or modulate transcription factor activity (Kung et al, 2013). Interestingly, it has been estimated that at least 50% of lncRNAs are expressed in the nervous system, and many exhibit cell-type specific patterns of neuronal expression (Quan et al, 2017; Qureshi and Mehler, 2013). …”