Protein synthesis in axons and terminals: significance for maintenance, plasticity and regulation of phenotype

Álvarez, Jaime; Giuditta, Antonio; Koenig, Edward

doi:10.1016/s0301-0082(99)00062-3

Cited by 174 publications

(178 citation statements)

References 397 publications

Supporting

Mentioning

167

Contrasting

Unclassified

Order By: Relevance

“…In fact, by the end of the nineteenth century it had already been hypothesized that axons might 'depend, as would seem a priori much more likely, for the most part upon autochthonous metabolism' [5]. This theory of intra-axonal protein synthesis remained for a long time a hotly debated issue, even long after protein synthesis in dendrites had been widely accepted (for a historical perspective see [6]). Only at the beginning of this century did work by Holt's group conclusively demonstrate that local protein synthesis is required for the chemotropic responses of axons to attractive and repulsive guidance cues [7].…”

Section: Intra-axonal Protein Synthesismentioning

confidence: 99%

Targeting Axonal Protein Synthesis in Neuroregeneration and Degeneration

Baleriola

Hengst

2015

Neurotherapeutics

View full text Add to dashboard Cite

Localized protein synthesis is a mechanism by which morphologically polarized cells react in a spatially confined and temporally acute manner to changes in their environment. During the development of the nervous system intra-axonal protein synthesis is crucial for the establishment of neuronal connections. In contrast, mature axons have long been considered as translationally inactive but upon nerve injury or under neurodegenerative conditions specific subsets of mRNAs are recruited into axons and locally translated. Intra-axonally synthesized proteins can have pathogenic or restorative and regenerative functions, and thus targeting the axonal translatome might have therapeutic value, for example in the treatment of spinal cord injury or Alzheimer's disease. In the case of Alzheimer's disease the local synthesis of the stress response transcription factor activating transcription factor 4 mediates the long-range retrograde spread of pathology across the brain, and inhibition of local Atf4 translation downstream of the integrated stress response might interfere with this spread. Several molecular tools and approaches have been developed to target specifically the axonal translatome by either overexposing proteins locally in axons or, conversely, knocking down selectively axonally localized mRNAs. Many questions about axonal translation remain to be answered, especially with regard to the mechanisms establishing specificity but, nevertheless, targeting the axonal translatome is a promising novel avenue to pursue in the development for future therapies for various neurological conditions.

show abstract

Section: Intra-axonal Protein Synthesismentioning

confidence: 99%

Targeting Axonal Protein Synthesis in Neuroregeneration and Degeneration

Baleriola

Hengst

2015

Neurotherapeutics

View full text Add to dashboard Cite

show abstract

“…[95][96][97] Growth cones have 500-1000 ribosomes that provide a low basal level of protein synthesis, but which yield a marked increase in local protein synthesis in response to NTs. Additional neurite extension could occur by the cannibalization of lipids and proteins from the proximal axon via the ubiquitin-proteosome pathway -that is, a localized redistribution of axonal membrane to allow compensatory synapse growth after CNS injury.…”

Section: Clinical Descriptionmentioning

confidence: 99%

Spinal shock revisited: a four-phase model

et al. 2004

View full text Add to dashboard Cite

Spinal shock has been of interest to clinicians for over two centuries. Advances in our understanding of both the neurophysiology of the spinal cord and neuroplasticity following spinal cord injury have provided us with additional insight into the phenomena of spinal shock. In this review, we provide a historical background followed by a description of a novel fourphase model for understanding and describing spinal shock. Clinical implications of the model are discussed as well.

show abstract

“…Strong evidence, however, has emerged in recent years showing local translation of proteins from existing mRNAs in the axon (Alvarez et al, 2000;Campenot and Eng, 2000;Piper and Holt, 2004). The only previously demonstrated role for axonal translation in synaptic plasticity is in the Aplysia (Martin et al, 1997;Sherff and Carew, 1999;Martin et al, 2000;Si et al, 2003), but, because the invertebrate axon is not as functionally specialized as the vertebrate axon, such work gives no indication of whether mammalian neurons, which have much more polarized processes, would also possess this capacity.…”

Section: Possible Role Of Local Axonal Translationmentioning

confidence: 99%

The Role of Protein Synthesis in Striatal Long-Term Depression

Yin¹,

Davis²,

Ronesi³

et al. 2006

J. Neurosci.

View full text Add to dashboard Cite

Long-term depression (LTD) at the corticostriatal synapse is postsynaptically induced but presynaptically expressed, the depression being a result of retrograde endocannabinoid signaling that activates presynaptic cannabinoid CB 1 receptors and reduces the probability of glutamate release. To study the role of protein synthesis in striatal LTD, we used a striatum-only preparation in which the presynaptic cell body is cut off, leaving intact only its axons, whose terminals synapse on medium spiny neurons. LTD (duration Ͼ150 min) was induced in this preparation, thus providing evidence that transcription in the presynaptic cell nucleus is not necessary for this form of plasticity. The maintenance of striatal LTD, however, was blocked by bath application of protein translation inhibitors but not by the same inhibitors loaded into the postsynaptic cell. These results suggest that local translation is critical for the expression of striatal LTD, distinguishing this form of mammalian synaptic plasticity from other forms that require postsynaptic protein synthesis. Possible roles of axonal or glial translation in striatal LTD are considered.

show abstract

Protein synthesis in axons and terminals: significance for maintenance, plasticity and regulation of phenotype

Cited by 174 publications

References 397 publications

Targeting Axonal Protein Synthesis in Neuroregeneration and Degeneration

Targeting Axonal Protein Synthesis in Neuroregeneration and Degeneration

Spinal shock revisited: a four-phase model

The Role of Protein Synthesis in Striatal Long-Term Depression

Contact Info

Product

Resources

About