Abstract
Axonal trajectories and neural circuit activities strongly rely on a complex system of molecular cues that finely orchestrate the patterning of neural commissures. Several of these axon guidance molecules undergo continuous recycling during brain development, according to incompletely understood intracellular mechanisms, that in part rely on endocytic and autophagic cascades. Based on their pivotal role in both pathways, lysosomes are emerging as a key hub in the sophisticated regulation of axonal guidance cue delivery, localization, and function. In this review, we will attempt to collect some of the most relevant research on the tight connection between lysosomal function and axon guidance regulation, providing some proof of concepts that may be helpful to understanding the relation between lysosomal storage disorders and neurodegenerative diseases.
Highlights
The development of the central nervous system (CNS) occurs during embryonic stages in a strictly temporally and spatially regulated manner, to allow for the organization of a network of nervous fibers that progressively increase the range of functional neuronal interactions
Ephrins were first discovered and described in the context of retinotopic mapping [18]. They are membrane-related guidance cues categorized into two classes: Ephrin-As (EphrinA1–Ephrin-A5), which are glycophosphatidylinositol (GPI)-anchored to the membrane, and Ephrin-Bs (Ephrin-B1–Ephrin-B3), which have a transmembrane domain followed by a short cytoplasmic domain [19]
Netrins are a family of laminin-related proteins that act in the extracellular compartment as chemotropic guidance cues during neuronal development
Summary
The development of the central nervous system (CNS) occurs during embryonic stages in a strictly temporally and spatially regulated manner, to allow for the organization of a network of nervous fibers that progressively increase the range of functional neuronal interactions. Understanding the cascade of molecular events occurring during both embryonic brain development and after brain injury could allow for the identification of druggable targets that may hamper neurodegenerative conditions and prevent the onset of irreversible cognitive decline in certain inherited disorders. In the past few years, lysosomes have attracted a remarkable interest for their key role in the Biomolecules 2021, 11, 191. Identification of druggable targets that may hamper neurodegenerative conditions prevent the onset of irreversible cognitive decline in certain inherited disorders. I past few years, lysosomes have attracted a remarkable interest for their key role i autophagic process during axonal remodeling [4]. We will try to briefly summarize the current knowled to briefly summarize the current knowledge of up-to-date discovered axonal guidance cues, up-to-date discovered axonal guidance cues, providing an inferential nexus bet providing an inferential nexus between their impaired activity and the brain pathogenesis their impaired activity and the brain pathogenesis of lysosomal storage disorders (L of lysosomal storage disorders (LSDs)
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