Abstract
Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration and death of motor neurons. This neurodegenerative disease leads to muscle atrophy, paralysis, and death due to respiratory failure. MicroRNAs (miRNAs) are small non-coding ribonucleic acids (RNAs) with a length of 19 to 25 nucleotides, participating in the regulation of gene expression. Different studies have demonstrated that miRNAs deregulation is critical for the onset of a considerable number of neurodegenerative diseases, including ALS. Some studies have underlined how miRNAs are deregulated in ALS patients and for this reason, design therapies are used to correct the aberrant expression of miRNAs. With this rationale, delivery systems can be designed to target specific miRNAs. Specifically, these systems can be derived from viral vectors (viral systems) or synthetic or natural materials, including exosomes, lipids, and polymers. Between many materials used for non-viral vectors production, the two-dimensional graphene and its derivatives represent a good alternative for efficiently delivering nucleic acids. The large surface-to-volume ratio and ability to penetrate cell membranes are among the advantages of graphene. This review focuses on the specific pathogenesis of miRNAs in ALS and on graphene delivery systems designed for gene delivery to create a primer for future studies in the field.
Highlights
Amyotrophic lateral sclerosis (ALS), known as motor neuron disease or Lou Gehrig’s disease, is a neurodegenerative affection caused by the degeneration and the death of motor neurons, responsible for carrying out muscle movements [1,2]
This review focuses on the specific pathogenesis of miRNAs in ALS and on graphene delivery systems designed for gene delivery to create a primer for future studies in the field
The biogenesis occurs with the excision of the upper part of the ribonucleic acids (RNAs) hairpin by the nuclear RNase III enzyme Drosha, which acts in concert with the DiGeorge Syndrome Critical Region 8 (DIGCR8) complex to generate 60–80 base pair chains with typical hairpin conformation know as precursor miRNAs (Figure 3) [19,23,24,25]
Summary
Amyotrophic lateral sclerosis (ALS), known as motor neuron disease or Lou Gehrig’s disease, is a neurodegenerative affection caused by the degeneration and the death of motor neurons, responsible for carrying out muscle movements [1,2]. Over 20 genes have been related to ALS, among these, mutations on Sod, tardbp, fus, c9orf, and pfn cause ~60–70% of the fALS cases and 10% of the sALS cases. Glutamate excitotoxicity, endoplasmic reticulum and oxidative stress, neuroinflammation, mitochondrial dysfunction, loss of trophic factors, and defects in axonal transport are proposed mechanisms that promote ALS progression [1] (Figure 2). Some miRNAs play an important role in the development and in the function of the motor neurons Alterations of these functions contribute to ALS neurodegeneration [9] and disease progression [10]. Comforting results in animal models have proved the role of miRNAs as therapeutic agents For this reason, new therapies and miRNAs delivery systems are being designed for ALS. The possibility of designing delivery strategies with graphene, a bidimensional nanomaterial with a high surface area and unique biological effects, will be discussed
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