Promoting axonal regeneration through exosomes: An update of recent findings on exosomal PTEN and mTOR modifiers

Exosomes, in the mix with other extracellular microvesicles (EVs), are very broadly implicated in a multitude of neuronal physiological and pathological processes. However, their roles in axonal regeneration upon injury, which is potentially useful from a therapeutics perspective, are less well-defined. Exosomes from both neuronal and non-neuronal sources have been shown to promote neurite growth or enhance axon regeneration of injured neurons. How these beneficial effects are actually achieved has not been very clear. In some cases the effects have been directly or indirectly attributed to specific exosome contents. These include microRNAs, polypeptides and various signaling molecules. The Phosphatase and tensin homologue (PTEN)-mechanistic target of rapamycin (mTOR) pathway is a key determinant of axonal regeneration. Recent works have uncovered novel molecules within exosomes and new findings on mechanisms of action whereby exosomes could enhance axonal regeneration by impinging on the PTEN-mTOR pathway. Here, an update of these recent findings is provided, and the cellular and molecular mechanisms of how some of these exosome-borne molecules could enhance axonal regeneration of injured neurons are reviewed and discussed.