Strategies for Spatial Proteome and Transcriptome Investigation in Adult Neuronal Axons

Neurons are highly asymmetric post-mitotic cells whose processes extend long distances to facilitate communication. Consequently, they encounter the complex problem of maintaining their structure and function over long distances. Over the last decade, research into the components composing the axon of a neuron has revealed the presence of local machinery of protein synthesis and deployment within different parts of the axon. However, there is still a need to understand how the endogenous proteome and transcriptome within the axon are distributed. The last decade has also witnessed a growth of technology capable of specifically labeling proteins and molecules of RNA. They are primarily based on gene editing techniques and recombinant antibody technology. Advances in technology now enable the delivery of large payloads of genetic material, paving the way for an in-depth investigation into the endogenous processes occurring within the axons of adult neurons. These capabilities open up exciting opportunities to address critical questions, potentially leading to new insights and strategies for treating neurodegenerative diseases. The review discusses different techniques available to a neuroscientist to help answer questions concerning the localization and transport of molecules within the axon. For instance, CRISPR is used to make specific changes to the genome and provide a means to tag endogenous proteins. Using these advances, in theory, it is possible to label molecules at scale and elucidate the role of different compartments that support protein synthesis and their subsequent deployment to specific regions within the axon.