MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression after transcription. These molecules play roles in many biological processes. MicroRNA-124 (mir-124) stands out as one of the most abundant miRNAs found in the brain. It is highly conserved across various species, suggesting its widespread importance in biological systems.
Core Biological Functions
Mir-124 is predominantly expressed in the central nervous system, with lower levels in other tissues. Its expression is particularly high in mature neurons, increasing as these cells differentiate and mature. This microRNA helps govern the transition from neural progenitor cells to neurons, promoting neuronal differentiation and inhibiting the proliferation of neural stem cells.
Mir-124 also contributes to the formation of neuronal structures, including neurites and synapses. It influences synaptic plasticity, which is the ability of synapses to strengthen or weaken over time in response to changes in activity. This regulation occurs by targeting specific genes that influence cellular processes such as cell survival, autophagy, and mitochondrial function.
Role in Neurological Conditions
Dysregulation of mir-124 is implicated in various neurological disorders. In conditions like Parkinson’s disease, reduced levels of mir-124 in plasma have been observed, and its activity influences processes such as neuroinflammation, oxidative stress, and mitochondrial dysfunction. In Alzheimer’s disease, mir-124 levels are downregulated in the brain, impacting the regulation of proteins involved in disease progression.
Mir-124 also plays a role in the context of stroke. Its levels can increase in the blood and brain following an acute ischemic stroke, and it has been explored for its potential to reduce brain damage and improve neurological outcomes. In brain tumors, including malignant gliomas, mir-124 expression is significantly depleted compared to healthy brain tissue, where its restoration can suppress tumor growth. Altered mir-124 expression is associated with depression, with increased levels found in the plasma of some depressed patients.
Broader Disease Implications
Mir-124 functions as a tumor suppressor in various cancers outside the brain, including breast, lung, colon, liver, and gastric cancers. Mir-124 can inhibit cell proliferation, promote programmed cell death, and suppress tumor spread by regulating target genes. Its altered expression is linked to bladder cancer, where it impacts proteins that drive tumor aggressiveness.
Mir-124 also shows relevance in inflammatory conditions. It can modulate inflammatory responses by influencing immune cell function. For instance, in allergic rhinitis, upregulation of mir-124 can alleviate allergy symptoms. Mir-124 also has roles in bone conditions like osteoporosis and osteosarcoma, where its expression levels are associated with disease progression and bone cell differentiation.
Therapeutic and Diagnostic Potential
Changes in mir-124 levels in bodily fluids like plasma or cerebrospinal fluid can indicate the presence or progression of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, and stroke. It also holds potential as a biomarker for cancers and bone conditions.
Strategies involving mir-124 aim to either restore its levels when low or inhibit its activity when overactive. Delivering mir-124 using nanoparticles has shown potential in reducing inflammation and promoting brain repair in models of Parkinson’s disease. In brain tumors, engineered viruses leveraging mir-124’s tumor-suppressive properties are being investigated. Developing mir-124-based therapies faces challenges, including precise delivery to target tissues and avoiding unintended side effects.