Neurons are highly polarized cells with long axons that can extend from millimeters to well over a meter in large vertebrates. Axons provide long-range connections between neurons and their target cells allowing the brain, spinal cord, and peripheral nerves to efficiently communicate. Given this long-distance separation, axons need a continuous supply of materials such as proteins, organelles, macromolecules, and mRNAs from the neuron soma to ensure their maturation, maintenance, and survival. With rates of fast axonal transport being relatively slow (1-3 µm/s), the distal axon must respond to environmental stimuli well before all the necessary materials can be delivered from the cell body. Therefore, localized protein synthesis of axonally transported transcripts provides an important mechanism to overcome this distance constraint. Highlighting their essential nature, disruption of axonal transport or axonal protein synthesis can cause axon development deficiencies or lead to axon degeneration.
Several RNA binding proteins linked to neurological diseases (e.g. TDP-43, FUS and SMN) have been detected in axons and they are thought to serve as carriers and protectants of transcripts as they are trafficked along axons. Furthermore, mutations in genes encoding components of the axonal transport machinery (e.g., kinesin KIF1A) are known to cause neurodevelopmental and neurodegenerative conditions. Similarly, impairments in axonal transport and localized protein synthesis unequivocally perturb axonal homeostasis and have been identified in diverse neurological diseases; however, it is often unclear exactly how this occurs, and it remains unknown whether disturbances in these key cellular processes are a primary cause or downstream consequence of neurodegeneration. Nevertheless, recent developments in the toolkit of axon-specific methods as well as in vivo imaging of live cellular processes are helping to improve our understanding of axon biology in both health and disease. With this Research Topic, we hope to showcase these advances and galvanize a field poised to generate a holistic understanding of the pathways and processes critical to maintaining axon integrity.
We therefore seek original research articles, reviews, methods, and mini-reviews on the genetic, molecular, and cellular mechanisms underpinning axonal development, function, and survival, with a specific focus on axonal transport and local protein synthesis. Key areas include, but are not restricted to:
• Axonal transport and the cytoskeleton
• Endolysosomal sorting and membrane trafficking
• Axonal injury
• Axonal protein synthesis
• Axon survival and neurodegeneration
• Axon regeneration
• Axonal mRNA storage mechanisms
• RNA-binding proteins and associated diseases
• Genetic and acquired peripheral neuropathies
Neurons are highly polarized cells with long axons that can extend from millimeters to well over a meter in large vertebrates. Axons provide long-range connections between neurons and their target cells allowing the brain, spinal cord, and peripheral nerves to efficiently communicate. Given this long-distance separation, axons need a continuous supply of materials such as proteins, organelles, macromolecules, and mRNAs from the neuron soma to ensure their maturation, maintenance, and survival. With rates of fast axonal transport being relatively slow (1-3 µm/s), the distal axon must respond to environmental stimuli well before all the necessary materials can be delivered from the cell body. Therefore, localized protein synthesis of axonally transported transcripts provides an important mechanism to overcome this distance constraint. Highlighting their essential nature, disruption of axonal transport or axonal protein synthesis can cause axon development deficiencies or lead to axon degeneration.
Several RNA binding proteins linked to neurological diseases (e.g. TDP-43, FUS and SMN) have been detected in axons and they are thought to serve as carriers and protectants of transcripts as they are trafficked along axons. Furthermore, mutations in genes encoding components of the axonal transport machinery (e.g., kinesin KIF1A) are known to cause neurodevelopmental and neurodegenerative conditions. Similarly, impairments in axonal transport and localized protein synthesis unequivocally perturb axonal homeostasis and have been identified in diverse neurological diseases; however, it is often unclear exactly how this occurs, and it remains unknown whether disturbances in these key cellular processes are a primary cause or downstream consequence of neurodegeneration. Nevertheless, recent developments in the toolkit of axon-specific methods as well as in vivo imaging of live cellular processes are helping to improve our understanding of axon biology in both health and disease. With this Research Topic, we hope to showcase these advances and galvanize a field poised to generate a holistic understanding of the pathways and processes critical to maintaining axon integrity.
We therefore seek original research articles, reviews, methods, and mini-reviews on the genetic, molecular, and cellular mechanisms underpinning axonal development, function, and survival, with a specific focus on axonal transport and local protein synthesis. Key areas include, but are not restricted to:
• Axonal transport and the cytoskeleton
• Endolysosomal sorting and membrane trafficking
• Axonal injury
• Axonal protein synthesis
• Axon survival and neurodegeneration
• Axon regeneration
• Axonal mRNA storage mechanisms
• RNA-binding proteins and associated diseases
• Genetic and acquired peripheral neuropathies
