Solvent Interaction Analysis: A New Lens for Protein Structure and Diagnostics.

Oligodendrocytes (OLs) are specialized glial cells in the central nervous system (CNS) responsible for forming the myelin sheath that wraps around neuronal axons. Myelin is crucial for the efficient transmission of electrical impulses along neurons. During development, neural progenitor cells (NPCs) in the CNS differentiate into oligodendrocyte progenitor cells (OPCs), which migrate throughout the brain and spinal cord. The OPCs then terminally differentiate into immature OLs. Upon receiving appropriate environmental cues, these immature OLs further mature, wrapping around nearby receptive axons and myelinating them []. Myelination of neuronal axons is essential for saltatory conduction of action potential, providing trophic support to the axons, and maintaining their survival and function. Consequently, loss of myelin integrity could lead to severe neurological disorders, such as multiple sclerosis, inherited leukodystrophies, and optic neuritis related to vision loss. To facilitate the repair of damaged myelin and maintain myelin integrity, it is important to understand the molecular mechanisms that regulate OL differentiation and maturation. The process of fate specification at NPC and OPC stages, as well as OL development and maturation, are controlled by several extrinsic and intrinsic factors, which regulate changes at both transcriptional and post-transcriptional levels. MicroRNAs (miRNAs) have been recognized as one of the key post-transcriptional regulators involved in determining the fate of NPCs and their transition into OPC and OL lineage [,]. MicroRNAs (miRNAs) are small, noncoding RNA molecules that are trimmed from longer hairpin-loop RNA sequences into functional 19–21 mers by the miRNA processing enzymes DICER1 and DROSHA []. miRNAs recognize a complementary sequence in the 3′ untranslated region (UTR) of a protein-coding messenger RNA (mRNA) and inhibit the expression of specific proteins, either by repressing RNA translation or directly promoting the degradation of the associated mRNAs []. Each miRNA can target multiple mRNAs, allowing them to modulate numerous pathways, and by regulating molecular pathways, miRNAs have the potential to modulate cell proliferation, differentiation, and lineage specification []. miRNAs play a critical role in the development of several CNS cell types, including neurons, astroglia, and oligodendrocyte lineage cells. The aberrant expression of several miRNAs has been implicated in a broad range of neurological disorders, including both demyelination and neurodegenerative diseases, where they may contribute to distinct but sometimes overlapping pathological processes []. Oligodendrocyte lineage progression is a dynamic developmental process involving sequential transitions from neural progenitors to OPCs, mature OLs, and myelinating OLs, with each stage characterized by distinct transcriptional and epigenetic programs. Given that miRNAs regulate gene expression in a context- and stage- specific manner, miRNA expression is likely to be temporally regulated to coordinate stage-specific cellular processes during OL development. Consistent with this notion, dynamic regulation of miRNAs in developing OLs has been documented in rodent models [], particularly by a study in which the deletion of Dicer in OPCs led to delayed OL differentiation and myelination []. This and several other studies have identified and confirmed the significance of specific miRNAs, such as miR219 and miR338, in OPC and OL differentiation and maturation [,]. However, most miRNA profiling and biochemical studies aimed at understanding the role of miRNAs in OPC and OL development have been performed using murine models. Although human and mouse OPCs and OLs share similarities, several important differences exist [,,], and a comprehensive profiling and characterization of stage-specific miRNA expression during human OL lineage cell (OLLC) development remains lacking.