Roles of mRNA Axonal Localization and Translation in Neurodegenerative Diseases

Excerpt

Neurons are highly polarized cells with processes that extend over a meter in humans, thus requiring careful management of the structural and metabolic needs of their network. Indeed, neurons need to tightly regulate the flux of information from the periphery to the center, and transport defects of a variety of peripheral signaling complexes, including endosomes, mitochondria, and mRNP granules, have been shown to result in neuronal degeneration. Axonal local translation has emerged as a way of maintaining axonal homeostasis and achieving signaling compartmentalization in neurons. Though an established hallmark of neuronal development and injury, axonal local translation has also been implicated in neurodegeneration and may be an important regulatory mechanism. Alteration in the local synthesis of key proteins involved in the establishment of neurodegenerative diseases and axonal survival could be central to the dying back phenomenon observed in neurodegenerative disorders, whereby axons degenerate before toxicity is manifested in the corresponding cell bodies. In this book chapter, we will briefly review the history and the mechanisms behind axonal translation and its involvement in neurodegenerative diseases.