Non-coding RNAs—Novel targets in neurotoxicity

Abstract

Over the past ten years non-coding RNAs (ncRNAs) have emerged as pivotal players in fundamental physiological and cellular processes and have been increasingly implicated in cancer, immune disorders, and cardiovascular, neurodegenerative, and metabolic diseases. MicroRNAs (miRNAs) represent a class of ncRNA molecules that function as negative regulators of post-transcriptional gene expression. miRNAs are predicted to regulate 60% of all human protein-coding genes and as such, play key roles in cellular and developmental processes, human health, and disease. Relative to counterparts that lack bindings sites for miRNAs, genes encoding proteins that are post-transcriptionally regulated by miRNAs are twice as likely to be sensitive to environmental chemical exposure. Not surprisingly, miRNAs have been recognized as targets or effectors of nervous system, developmental, hepatic, and carcinogenic toxicants, and have been identified as putative regulators of phase I xenobiotic-metabolizing enzymes. In this review, we give an overview of the types of ncRNAs and highlight their roles in neurodevelopment, neurological disease, activity-dependent signaling, and drug metabolism. We then delve into specific examples that illustrate their importance as mediators, effectors, or adaptive agents of neurotoxicants or neuroactive pharmaceutical compounds. Finally, we identify a number of outstanding questions regarding ncRNAs and neurotoxicity.

Effects of organic and inorganic mercury(II) on gene expression via DNA conformational changes

“…Transcriptional repression has been reported to induce atypical neuronal cell death that is distinct from apoptosis, necrosis, or autophagy (Hoshino et al, 2006). In addition to protein expression via mRNA synthesis, transcription contributes gene regulation via non-coding RNAs (Tal and Tanguay, 2012) and genomic stability via transcription-coupled DNA repair (Jaarsma et al, 2011). Together with our present study, these results suggest that aberrant transcription of Hg-bound DNA underlies the neurotoxic mechanisms of Hg.…”

Overlapped Metabolic and Therapeutic Links between Alzheimer and Diabetes

“…The noncoding RNAs are also involved in synapses, neuronal specification and differentiation, and regulation of dendritic spine development. So their damage due to oxidative stress contributes to development of neurodegenerative diseases, especially AD [302][303][304]. Nunomura et al [303] extensively has reviewed the RNA oxidation in neurodegenerative diseases and has discussed the biological significance and cellular mechanisms that protect against RNA oxidation.…”

Coding and noncoding expression patterns associated with rare obesity-related disorders: Prader–Willi and Alström syndromes

“…35–40 miRNAs regulate and target most protein-coding genes in the human genome, with multiple classes highly expressed in the nervous system. 25,41 They actively participate in neuronal development, function, and network activity.…”