MicroRNA Dynamics in Neurodegenerative Disease Pathogenesis

MicroRNAs are short non-coding RNA molecules that fine-tune gene expression by binding complementary sequences in target messenger RNAs, leading to translational repression or mRNA degradation. In the central nervous system, microRNAs orchestrate critical processes including neuronal differentiation, synaptic plasticity and the stress response. Dysregulation of microRNA biogenesis or function has emerged as a central feature of neurodegenerative disorders. Aberrant microRNA expression can promote accumulation of misfolded proteins, disturb mitochondrial homeostasis and impair autophagic clearance, thereby accelerating neuronal death. In parallel, altered microRNA profiles in cerebrospinal fluid and peripheral blood have shown promise as minimally invasive biomarkers for early detection and disease monitoring. Beyond diagnostics, targeted modulation of specific microRNAs using mimics or inhibitors offers a novel therapeutic avenue to restore proteostasis, dampen neuroinflammation and support neuronal survival. Taken together, advances in understanding microRNA dynamics illuminate their dual role as both drivers of pathogenesis and tools for intervention in conditions such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and Huntington’s disease.

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MicroRNA Dynamics in Neurodegenerative Disease Pathogenesis publication trend

The graph below shows the total number of articles in microrna dynamics in neurodegenerative disease pathogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

MicroRNA: Short non-coding RNA molecules that regulate gene expression post-transcriptionally.

Neuroinflammation: Inflammatory response within the nervous system, often mediated by microglia and astrocytes.

Autophagy: Intracellular degradation pathway that recycles damaged organelles and misfolded proteins via lysosomes.

Oxidative stress: State in which reactive oxygen species overwhelm endogenous antioxidant defences.

Substantia nigra: Midbrain structure rich in dopaminergic neurons, critically involved in motor control.

References

1. MicroRNA-218-5p-Ddx41 axis restrains microglia-mediated neuroinflammation through downregulating type I interferon response in a mouse model of Parkinson’s disease. Journal of Translational Medicine (2024).
2. miR-214-3p promotes the pathogenesis of Parkinson's disease by inhibiting autophagy. Biomedicine & Pharmacotherapy (2024).
3. Interplay between MicroRNAs and Oxidative Stress in Neurodegenerative Diseases. International Journal of Molecular Sciences (2019).