Unraveling the Complex Role of Non-Coding RNAs in Neurodegenerative Diseases

Dear Colleagues,

Neurodegenerative diseases (NDs) are a group of progressive disorders marked by the degeneration of neurons in the central nervous system, resulting in cognitive decline, motor impairments, and behavioral changes. Predominantly affecting the aging population, conditions such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS) have been key research focuses for decades. Despite extensive investigations, the causes of NDs remain unclear, and the search for effective therapeutic interventions continues to pose significant challenges in modern medicine. The emerging field of non-coding RNA (ncRNA) research has brought new insights into the pathogenesis of NDs, revealing potential mechanisms and therapeutic targets.

NcRNAs, which include microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), regulate gene expression through a variety of epigenetic, transcriptional, and post-transcriptional mechanisms. These regulatory molecules are crucial for neural cell differentiation and synaptic plasticity, both of which are disrupted in NDs. For example, specific miRNAs, such as miR-132 and miR-129, have been linked to Alzheimer's disease by influencing the accumulation of amyloid-beta and tau proteins. LncRNAs have also been associated with the pathogenesis of Alzheimer's and Parkinson's diseases, indicating a broader role for ncRNAs in ND pathology.

The diagnostic and therapeutic potential of ncRNAs is becoming increasingly recognized, with these molecules being identified as promising biomarkers for early detection and monitoring of disease progression in NDs. The possibility of modulating ncRNA expression to develop targeted therapies represents an exciting frontier in research. However, the complex interactions among ncRNAs and the heterogeneity of NDs present significant challenges for clinical application.

It is estimated that approximately 90% of the human genome is transcribed into ncRNAs that do not code for proteins. This extensive range of non-coding RNAs encompasses a variety of functions that remain largely unexplored. For instance, the primary roles of lncRNAs are still not fully understood, though the current research suggests that they may compete with miRNAs for binding sites, thus influencing gene expression regulation. Given the complexity of miRNAs—where one miRNA can regulate hundreds of genes, and a single gene can be targeted by multiple miRNAs—the interactions between these molecules represent a critical area of investigation. Understanding these interactions is essential for leveraging the therapeutic potential of ncRNAs in the management of neurodegenerative diseases.

Further research is crucial to unravel the complex network of ncRNA interactions and to fully harness their potential for the diagnosis, treatment, and prevention of neurodegenerative diseases. This endeavor will require a multidisciplinary approach that integrates genomics, molecular biology, and computational biology to illuminate the enigmatic roles of ncRNAs in NDs and pave the way for more effective clinical interventions.

Prof. Dr. Stephen Massa
Dr. Atsushi Mizuma
Dr. Jian Shi
Guest Editors

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• miRNA
• lncRNA
• neurodegenerative diseases
• Alzheimer’s disease
• Parkinson disease