Tiny RNA Molecules That Help Build and Repair the Brain
2017 Scientific Review
Original Paper: “MicroRNA: Basic Concepts and Implications for Regeneration and Repair of Neurodegenerative Diseases”
Saraiva C., Esteves M., Bernardino L. • Biochemical Pharmacology • October 2017
What Is This Paper About?
This is a review article — a careful summary of what scientists knew in 2017 about tiny molecules called microRNAs (miRNAs) and how they influence the brain. The authors explain the basic science of miRNAs and then focus on how these molecules help create new brain cells (neurogenesis) and how their disruption contributes to major neurodegenerative diseases.
They also discuss whether miRNAs could one day be used as tools to diagnose or treat conditions such as Alzheimer’s, Parkinson’s, Huntington’s disease, and amyotrophic lateral sclerosis (ALS).
Basic Concepts: What Are microRNAs?
MicroRNAs are very short pieces of RNA (about 20–25 building blocks long) that do not code for proteins. Instead, they act as molecular “dimmer switches.” Each miRNA can attach to many different messenger RNAs and reduce or silence the production of the corresponding proteins.
Scientists estimate that miRNAs help control roughly 30% of all human genes. Because of this broad reach, they influence many essential processes:
- Whether a young brain cell survives
- How it matures into a specialized neuron
- How well neurons connect and communicate
- How the brain responds to injury or disease
miRNAs are made through a multi-step process inside the cell and are then loaded into a protein machine that helps them find and silence their target genes. Their levels can be finely tuned, which makes them powerful regulators of brain development and maintenance.
Four Key microRNAs in the Brain
The review pays special attention to four miRNAs that are especially important for both building new neurons and for disease processes:
miR-9
Helps decide the fate of neural stem cells and guides their migration. It is often altered in Alzheimer’s and other neurodegenerative conditions.
miR-124
One of the most abundant miRNAs in the adult brain. It strongly promotes the maturation of neural stem cells into neurons and supports healthy synaptic connections. Changes in miR-124 are linked to several neurodegenerative diseases.
miR-132
Important for learning, memory, and the growth of connections between neurons. Its levels drop in Alzheimer’s disease and some other conditions, which may contribute to cognitive decline.
miR-137
Helps keep neural stem cells in a balanced state and influences differentiation. It has been linked to both neurogenesis and risk for certain psychiatric and neurodegenerative disorders.
The Link Between Making New Neurons and Losing Them
Adult brains can still generate a limited number of new neurons in specific regions (a process called adult neurogenesis). The same miRNAs that guide this healthy process are frequently disrupted in neurodegenerative diseases.
When these miRNAs go out of balance, two problems can occur at once:
- Fewer new neurons are produced or the new ones fail to mature properly.
- Existing neurons become more vulnerable to stress, inflammation, protein clumps, or other disease-related damage.
This dual role — supporting both regeneration and vulnerability — makes these miRNAs especially interesting as potential therapeutic targets.
What the Review Says About Major Diseases
Alzheimer’s disease: Several of the key miRNAs (especially miR-9, miR-124, and miR-132) are altered. These changes may contribute to synapse loss, the buildup of toxic proteins, and failure to generate replacement neurons.
Parkinson’s disease: miRNA imbalances affect the survival of dopamine-producing neurons and the brain’s ability to respond to injury.
Huntington’s disease: Specific miRNA changes appear early and may influence both the toxic effects of the mutant huntingtin protein and the capacity for neural repair.
ALS (amyotrophic lateral sclerosis): miRNAs that normally support motor neuron health and glial cell function are disrupted, contributing to progressive nerve-cell death.
Can We Use microRNAs as Medicines or Tests?
The authors discuss two main clinical possibilities:
1. Biomarkers (Diagnostic Clues)
Because miRNAs circulate in blood, cerebrospinal fluid, and other body fluids and remain relatively stable, their levels can serve as early warning signals or disease-stage indicators. Different patterns of miRNA changes may help distinguish between neurodegenerative diseases or track how a patient is progressing.
2. Therapeutic Tools
Scientists can try to restore healthy miRNA levels by:
- Delivering synthetic versions of beneficial miRNAs (miRNA mimics)
- Blocking harmful miRNAs with complementary molecules called antagomirs or anti-miRs
In animal studies, adjusting certain miRNAs has improved neuron survival, reduced inflammation, and even supported the generation of new neurons. However, safely and effectively delivering these molecules to the right brain cells remains a major technical challenge.
Limitations and Challenges
- miRNAs affect many genes at once, so changing one can have unintended side effects.
- Delivering RNA-based therapies across the blood–brain barrier is difficult.
- Different patients and different disease stages may require different miRNA adjustments.
- Most evidence in 2017 still came from laboratory models; large, carefully controlled human trials were still needed.
The Bottom Line
MicroRNAs are powerful, tiny regulators that help the brain build new neurons and keep existing ones healthy. When their levels go wrong, they contribute to the progressive loss of nerve cells seen in Alzheimer’s, Parkinson’s, Huntington’s, and ALS. Because the same molecules that support regeneration are often disrupted in disease, restoring their balance is an attractive long-term goal for both diagnosis and treatment.
This 2017 review provided a clear roadmap of the basic biology and the therapeutic potential of miRNAs in brain repair — ideas that continue to guide research today.
Source
Saraiva, C., Esteves, M., & Bernardino, L. MicroRNA: Basic concepts and implications for regeneration and repair of neurodegenerative diseases. Biochemical Pharmacology, 141, 118–131 (2017).
DOI: 10.1016/j.bcp.2017.07.008 | PMID: 28709951
This summary was prepared in plain language for general understanding and does not replace the original scientific publication or medical advice.
