MicroRNAs and Long Non-Coding RNAs Affect the Mechanisms Involved in Age-Related Neurodegeneration in a Manner Depending on RNA-Binding Proteins.

Mehrdad Hashemi, Pezhman Shafiei Asheghabadi, Mahdi Moassesfar, Saba Mashhadikhan, Sevda Nasirzade, Ali Vasheghani Farahani, Shaghayegh Mehdizadeh, Shinoo Minaei, Maryam Rahmani, Faranak Jamshidian, Najma Farahani, Russel J Reiter, Afshin Taheriazam, Farzaneh Hasani Sadi, Kiavash Hushmandi, Mina Alimohammadi, Payman Rahimzadeh, Maliheh Entezari

Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital, Faculty of Medicine, TeMs.C., Islamic Azad University, Tehran, Iran. · pubmed

Paper

Abstract

Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), are marked by progressive neuronal loss and aberrant protein aggregation, presenting substantial global healthcare challenges. Recent research has illuminated the pivotal roles of RNA-binding proteins (RBPs) and non-coding RNAs (ncRNAs), notably microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in the molecular pathogenesis of age-related neurodegeneration. RBPs orchestrate RNA metabolism and engage extensively with miRNAs and lncRNAs to modulate gene expression at the post-transcriptional level. Dysregulation of these interactions precipitates pathological phenomena such as protein misfolding, stress granule formation, and disrupted RNA processing, thereby exacerbating neuronal dysfunction and death. Specific miRNAs have been implicated in regulating key neurodegenerative biomarkers, including tau and amyloid-β in AD, motor neuron maintenance in ALS, and survival pathways in HD. Elucidating the intricate interplay between RBPs and ncRNAs holds significant promise for the development of therapeutic strategies aimed at ameliorating RNA-mediated mechanisms in neurodegenerative disorders.

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Research summary

The paper claims that the dysregulation of RNA-binding proteins and non-coding RNAs contributes to the mechanisms of age-related neurodegeneration. This research is relevant as it explores the molecular underpinnings of neurodegenerative diseases, which are significant aspects of aging and could lead to potential therapeutic strategies that address root causes rather than just symptoms.

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