A Review on the Role of Endogenous Neurotrophins and Schwann Cells in Axonal Regeneration

Injury to the peripheral nerve is traditionally referred to acquired nerve injury as they are the result of physical trauma due to laceration, stretch, crush and compression of nerves. However, peripheral nerve injury may not be completely limited to acquired physical trauma. Peripheral nerve injury equally implies clinical conditions like Guillain-Barré syndrome (GBS), Carpal tunnel syndrome, rheumatoid arthritis and diabetes. Physical trauma is commonly mono-neuropathic as it engages a single nerve and produces focal damage, while in the context of pathological conditions the damage is divergent involving a group of the nerve causing polyneuropathy. Damage to the peripheral nerve can cause a diverse range of manifestations from sensory impairment to loss of function with unpredictable recovery patterns. Presently no treatment option provides complete or functional recovery in nerve injury, as nerve cells are highly differentiated and inert to regeneration. However, the regenerative phenotypes in Schwann cells get expressed when a signalling cascade is triggered by neurotrophins. Neurotrophins are one of the promising biomolecules that are released naturally post-injury with the potential to exhibit better functional recovery. Pharmacological intervention modulating the expression of these neurotrophins such as brain-derived neurotrophic factor (BDNF) and pituitary adenylyl cyclase-activating peptide (PACAP) can prove to be a significant treatment option as endogenous compounds which may have remarkable innate advantage showing maximum ‘biological relevance’. Graphical abstract: [Figure not available: see fulltext.]