Long Non-coding RNAs in Pathogenesis of Neurodegenerative Diseases

Abstract

Emerging evidence addresses the link between the aberrant epigenetic regulation of gene expression and numerous diseases including neurological disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). LncRNAs, a class of ncRNAs, have length of 200 nt or more, some of which crucially regulate a variety of biological processes such as epigenetic-mediated chromatin remodeling, mRNA stability, X-chromosome inactivation and imprinting. Aberrant regulation of the lncRNAs contributes to pathogenesis of many diseases, such as the neurological disorders at the transcriptional and post-transcriptional levels. In this review, we highlight the latest research progress on the contributions of some lncRNAs to the pathogenesis of neurodegenerative diseases via varied mechanisms, such as autophagy regulation, Aβ deposition, neuroinflammation, Tau phosphorylation and α-synuclein aggregation. Meanwhile, we also address the potential challenges on the lncRNAs-mediated epigenetic study to further understand the molecular mechanism of the neurodegenerative diseases.

Signaling by LncRNAs: Structure, Cellular Homeostasis, and Disease Pathology

“…The central nervous system possesses the largest number of lncRNAs, which constitutes almost 40% of the total lncRNAs present in the human body [ 26 ]. They show greater conservation in the brain, along with the highest degree of spatial and temporal specificities than any other locations in the human body [ 104 ]. Under normal physiological conditions, lncRNAs regulate the development and differentiation of the neuronal cells and the nervous system.…”

Non-Coding RNAs as Novel Regulators of Neuroinflammation in Alzheimer’s Disease

“…lncRNA is highly expressed in mammalian neural tissue, enabling it to respond quickly to environmental and molecular changes. In addition, lncRNAs participate in the physiological processes of a variety of neurodegenerative diseases such as AD, Parkinson’s disease, and Huntington’s disease ( 111 – 113 ). Neuroinflammation is an important factor driving deterioration in various neurodegenerative diseases.…”

Long noncoding RNAs as regulators of pediatric acute myeloid leukemia

“…Given their versatile cellular and molecular functions, it is no surprise that lncRNAs are involved in many essential physiological processes such as genomic imprinting and differentiation, as well as in the pathogenesis of diseases such as cancer, neurodegenerative disorders, and metabolomic diseases [ 31 – 33 ].…”