Adult Neural Stem Cell Regulation by Small Non-coding RNAs: Physiological Significance and Pathological Implications

Abstract

The adult neurogenic niches are complex multicellular systems, receiving regulatory input from a multitude of intracellular, juxtacrine, and paracrine signals and biological pathways. Within the niches, adult neural stem cells (aNSCs) generate astrocytic and neuronal progeny, with the latter predominating in physiological conditions. The new neurons generated from this neurogenic process are functionally linked to memory, cognition, and mood regulation, while much less is known about the functional contribution of aNSC-derived newborn astrocytes and adult-born oligodendrocytes. Accumulating evidence suggests that the deregulation of aNSCs and their progeny can impact, or can be impacted by, aging and several brain pathologies, including neurodevelopmental and mood disorders, neurodegenerative diseases, and also by insults, such as epileptic seizures, stroke, or traumatic brain injury. Hence, understanding the regulatory underpinnings of aNSC activation, differentiation, and fate commitment could help identify novel therapeutic avenues for a series of pathological conditions. Over the last two decades, small non-coding RNAs (sncRNAs) have emerged as key regulators of NSC fate determination in the adult neurogenic niches. In this review, we synthesize prior knowledge on how sncRNAs, such as microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs), may impact NSC fate determination in the adult brain and we critically assess the functional significance of these events. We discuss the concepts that emerge from these examples and how they could be used to provide a framework for considering aNSC (de)regulation in the pathogenesis and treatment of neurological diseases.

Emerging Roles of RNA-Binding Proteins in Neurodevelopment

“…Should these properties go awry, proper development of an organism can be interrupted. For example, mutations in certain stem cell regulatory pathways have been shown to promote hyperplastic growth, whereas others lead to a decrease in the stem cell pool [ 13 , 14 , 15 ]. These events may lead to problems later in development and could contribute to several diseases including cancer.…”

Combinational treatments of RNA interference and extracellular vesicles in the spinocerebellar ataxia

“…Artificial miRNAs can target disease genes ( Saad et al, 2021 ). They are important for brain development and homeostasis ( Penning et al, 2021 ). The imbalance of miRNAs is closely related to the pathogenesis of NDs, which may be the biomarkers.…”

Piwil2 (Mili) sustains neurogenesis and prevents cellular senescence in the postnatal hippocampus

“…Moreover, TE expression increases following the differentiation of NPC (Muotri et al , 2005 ), in parallel with the number of somatic TE insertions found in hippocampal neurons (Upton et al , 2015 ), arguing against functions of the piRNA pathway in postmitotic nerve cells. Given that the hippocampus is one of the niches in which neurogenesis persists beyond embryonic age, we hypothesize that the piRNA pathway may be present in aNPCs, possibly contributing to maintain the neurogenesis capacity lifelong (Penning et al , 2022 ).…”