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Non-coding RNAs in neurodegeneration: an axis-based, evidence-tiered mechanistic synthesis
Non-coding RNAs and their roles in brain cell degeneration: a structured review of evidence
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Abstract
An evidence-tiered framework integrating microRNAs, long non-coding RNAs, and circular RNAs across major neurodegenerative disorders is proposed.
- Non-coding RNAs (ncRNAs) may influence neuronal plasticity and susceptibility in various diseases.
- Categorization of studies along four axes—proteostasis/protein aggregation, neuroinflammation, synaptic/circuit dysfunction, and mitochondrial/autophagy dysfunction—facilitates cross-disease comparison.
- Common regulatory modules include miRNAs modulating autophagy and inflammatory-metabolic coupling, lncRNAs regulating amyloid/synuclein-related processes, and circRNA-mediated interactions with miRNAs and RNA-binding proteins.
- NcRNAs have been associated with bioenergetic stress, impacting glial cell function, neuronal survival, and metabolic vulnerability.
- Challenges such as evidence heterogeneity, cell-type specificity, blood-brain barrier constraints, and off-target effects may hinder the development of ncRNA-based biomarkers and therapeutics.
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