Abstract
Oxidative stress (OS) results from an imbalance between the production of reactive oxygen species and the cellular antioxidant capacity. OS plays a central role in neurodegenerative diseases, where the progressive accumulation of reactive oxygen species induces mitochondrial dysfunction, protein aggregation and inflammation. Regulatory non-protein-coding RNAs (ncRNAs) are essential transcriptional and post-transcriptional gene expression controllers, showing a highly regulated expression in space (cell types), time (developmental and ageing processes) and response to specific stimuli. These dynamic changes shape signaling pathways that are critical for the developmental processes of the nervous system and brain cell homeostasis. Diverse classes of ncRNAs have been involved in the cell response to OS and have been targeted in therapeutic designs. The perturbed expression of ncRNAs has been shown in human neurodegenerative diseases, with these changes contributing to pathogenic mechanisms, including OS and associated toxicity. In the present review, we summarize existing literature linking OS, neurodegeneration and ncRNA function. We provide evidences for the central role of OS in age-related neurodegenerative conditions, recapitulating the main types of regulatory ncRNAs with roles in the normal function of the nervous system and summarizing up-to-date information on ncRNA deregulation with a direct impact on OS associated with major neurodegenerative conditions.
Highlights
Neurodegenerative disorders are a heterogeneous class of diseases characterized by a slow, progressive neuronal dysfunction and loss
The above reviewed results emphasize the relevance of regulatory non-protein-coding RNAs (ncRNAs) as bioactive molecules regulating the management of oxidative stress (OS) in neurodegenerative conditions
We are aware that additional ncRNA classes present in the central nervous system (CNS) can be affected by and associated to OS and neurodegeneration, including highly abundant ribosomal RNAs (rRNAs)
Summary
Neurodegenerative disorders are a heterogeneous class of diseases characterized by a slow, progressive neuronal dysfunction and loss. NcRNAs are especially abundant and diverse in the central nervous system (CNS), showing a highly specific and dynamic temporal and spatial expression pattern that guides neurodevelopmental processes, including neural stem cell proliferation and differentiation [6,7]. In addition to their role in developmental processes, ncRNAs are key for the maintenance and normal functioning of adult, post-mitotic neurons. We will provide an overview on the functional association between ncRNAs and the response to OS, a major hallmark in neurodegenerative disorders, and we will review the OS–ncRNA axis in major neurodegenerative conditions
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