Targeting Axonal Protein Synthesis in Neuroregeneration and Degeneration

Neurotherapeutics, 2015 · DOI: 10.1007/s13311-014-0308-8 · Published: November 5, 2014

Simple Explanation

Localized protein synthesis allows cells to react quickly to environmental changes. In nerve cells, this is vital for forming connections during development. Mature nerve axons, once thought inactive, can also synthesize proteins locally upon injury or in neurodegenerative diseases. These locally made proteins can either help repair damage or contribute to disease. Targeting this protein synthesis could be a way to treat conditions like spinal cord injury or Alzheimer’s disease. Scientists are developing tools to specifically target protein synthesis in axons. While many questions remain, manipulating axonal protein synthesis is a promising approach for treating neurological disorders.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Intra-axonal protein synthesis is crucial for growth cone behavior, axonal pathfinding, axon maintenance, and retrograde signaling in developing axons.
2
Local synthesis of ATF4 transmits a neurodegenerative signal across brain regions in Alzheimer's disease.
3
Exposure of axons to Aβ1-42 triggers the recruitment of a specific cohort of mRNAs that is unique to the exposure of distal axons to oligomeric Aβ1-42.

Research Summary

The review discusses the role of localized protein synthesis in axons, highlighting its importance in both neuroregeneration and neurodegeneration. It explores how intra-axonal translation is reactivated after nerve injury and in neurodegenerative diseases like Alzheimer's, and how this process can be targeted for therapeutic purposes. The authors also examine molecular tools and approaches to manipulate the axonal translatome, offering insights into potential future therapies for various neurological conditions.

Practical Implications

Therapeutic Target for Neurological Disorders

Targeting axonal protein synthesis offers a novel avenue for developing therapies for conditions like spinal cord injury, Alzheimer's disease, ALS and SMA.

Understanding Disease Mechanisms

Investigating the axonal translatome can provide invaluable insight into pathological changes induced by neurodegenerative stimuli, leading to a better understanding of disease mechanisms.

Development of Specific Therapeutic Tools

The review highlights the need for developing tools that selectively modify the axonal transcriptome or translatome to avoid unwanted side effects in other neuronal compartments.

Study Limitations

1
Specificity mechanisms of local translation are still largely unknown.
2
The role of many localized transcripts in vivo remains an open question.
3
Current targeting of axonal protein synthesis is far from clinical application.

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