Retinoic acid (RA) is involved in the induction of neural differentiation, motor neuron axon outgrowth and neural patterning during development, but there is growing evidence that RA could be used as a therapeutic molecule for the induction of axon regeneration and the treatment of neurodegeneration.
RA is a metabolic product of vitamin A (retinol) that signals in both a paracrine and an autocrine manner.
During development, RA is required for hindbrain patterning and, together with sonic hedgehog and bone morphogenetic proteins, for patterning the dorsoventral axis of the neural tube.
RA also induces the differentiation of various types of neurons and glia, by activating the transcription of genes that encode various transcription factors, cell signalling molecules, structural proteins, enzymes and cell-surface receptors. This ability can be harnessed to induce the differentiation of stem cells into neural cell types, which could then be used for therapeutic transplantation.
In peripheral nerves, RA stimulates the regenerative response. In this case it does not necessarily act directly on the neuron: Schwann cells and macrophages might be targets of RA.
In the mature CNS, RA has a role in the maintenance of plasticity and neural stem cell production. Together with data that implicate a loss of RA signalling in the aetiology of Parkinson's disease, motor neuron disease and Alzheimer's disease, these findings highlight the potential of RA replacement as a therapeutic strategy for treating these conditions.
Retinoic acid (RA) is involved in the induction of neural differentiation, motor axon outgrowth and neural patterning. Like other developmental molecules, RA continues to play a role after development has been completed. Elevated RA signalling in the adult triggers axon outgrowth and, consequently, nerve regeneration. RA is also involved in the maintenance of the differentiated state of adult neurons, and disruption of RA signalling in the adult leads to the degeneration of motor neurons (motor neuron disease), the development of Alzheimer's disease and, possibly, the development of Parkinson's disease. The data described here strongly suggest that RA could be used as a therapeutic molecule for the induction of axon regeneration and the treatment of neurodegeneration.
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The author declares no competing financial interests.
Blocks of mesoderm located adjacent to the neural tube that develop into the vertebral column and its associated muscles.
Segmental units of the developing hindbrain.
An opening created by surgical means between two normally separate tissues.
- Dorsal root entry zone
The region where peripheral nerves enter the spinal cord. It marks the border between the PNS and the CNS.
The inability to smell.
- Proamnesic molecule
A compound that improves memory.
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Maden, M. Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat Rev Neurosci 8, 755–765 (2007). https://doi.org/10.1038/nrn2212
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