Axonal Organelles as Molecular Platforms for Axon Growth and Regeneration after Injury

Abstract

Investigating the molecular mechanisms governing developmental axon growth has been a useful approach for identifying new strategies for boosting axon regeneration after injury, with the goal of treating debilitating conditions such as spinal cord injury and vision loss. The picture emerging is that various axonal organelles are important centers for organizing the molecular mechanisms and machinery required for growth cone development and axon extension, and these have recently been targeted to stimulate robust regeneration in the injured adult central nervous system (CNS). This review summarizes recent literature highlighting a central role for organelles such as recycling endosomes, the endoplasmic reticulum, mitochondria, lysosomes, autophagosomes and the proteasome in developmental axon growth, and describes how these organelles can be targeted to promote axon regeneration after injury to the adult CNS. This review also examines the connections between these organelles in developing and regenerating axons, and finally discusses the molecular mechanisms within the axon that are required for successful axon growth.

The Role of Lipids, Lipid Metabolism and Ectopic Lipid Accumulation in Axon Growth, Regeneration and Repair after CNS Injury and Disease

“…In addition, spatial and temporal alteration of circulating fatty acids may compromise CNS function and repair under pathological conditions including CNS trauma and neurodegenerative diseases. Correct positioning of organelles for membrane trafficking, lipid exchange and energy production requires a complex interplay between various organelles and molecular motors [ 249 ]. The fabrication of new inducible and reversible systems may allow us to gain spatiotemporal control over this process [ 250 ], enabling CNS repair with precision.…”

Traction of 3D and 4D Printing in the Healthcare Industry: From Drug Delivery and Analysis to Regenerative Medicine

“…Previous studies have indicated significant developments in tissue-engineered conduits integration to bridge defects of spinal cord injury using various strategies such as cell transplants, degradation products of glial scar or biological cues, and physical guides. − The tissue of the spinal cord is not structurally homogeneous but consists of various types of neural cells organized in spatially complex orders. , The locally definite neuronal subtypes firmly affect axonal growth . Consequently, successfully recreating/fabricating patient-specific structures in appropriate clinical shape, size, and structural integrity has progressed by integrating progenitor and neural stem cells with biocompatible 3D-printed scaffolds to evaluate novel therapeutic cues for injuries in the spinal cord. ,,,,− Three-dimensional printing approaches are applied in two distinct fields of spinal cord scaffold development: (i) seeding of cells on 3D-printed scaffolds and (ii) 3D printing of bioinks for construct fabrication.…”

LRRK2 along the Golgi and lysosome connection: a jamming situation

“…Instead, the membrane sources allowing axonal growth are less characterized. However, complementary observations suggest a role for late and recycling endosomes via mechanisms involving several Rab proteins, including the LRRK2 substrates Rab8 and Rab5 (albeit evidence is weaker for the latter; reviewed in [ 54 ]).…”