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Axons in the peripheral nervous system have the ability to repair themselves after damage, whereas axons in the central nervous system are unable to do so. A common and important characteristic of damage to the spinal cord, brain, and peripheral nerves is the disruption of axonal regrowth. Interestingly, intrinsic growth factors play a significant role in the axonal regeneration of injured nerves. Various factors such as proteomic profile, microtubule stability, ribosomal location, and signalling pathways mark a line between the central and peripheral axons’ capacity for self-renewal. Unfortunately, glial scar development, myelin-associated inhibitor molecules, lack of neurotrophic factors, and inflammatory reactions are among the factors that restrict axonal regeneration. Molecular pathways such as cAMP, MAPK, JAK/STAT, ATF3/CREB, BMP/SMAD, AKT/mTORC1/p70S6K, PI3K/AKT, GSK-3β/CLASP, BDNF/Trk, Ras/ERK, integrin/FAK, RhoA/ROCK/LIMK, and POSTN/integrin are activated after nerve injury and are considered significant players in axonal regeneration. In addition to the aforementioned pathways, growth factors, microRNAs, and astrocytes are also commendable participants in regeneration. In this review, we discuss the detailed mechanism of each pathway along with key players that can be potentially valuable targets to help achieve quick axonal healing. We also identify the prospective targets that could help close knowledge gaps in the molecular pathways underlying regeneration and shed light on the creation of more powerful strategies to encourage axonal regeneration after nervous system injury.

Background The present study aimed to prepare effective silk derived formulations in combination with plant extract (Aloe vera gel) to speed up the wound healing process in diabetic mice. Methods Diabetes was induced in albino mice by using alloxan monohydrate. After successful induction of diabetes in mice, excision wounds were created via biopsy puncture (6 mm). Wound healing effect of silk sericin (5%) and silk fibroin (5%) individually and in combination with 5% Aloe vera gel was evaluated by determining the percent wound contraction, healing time and histological analysis. Results The results indicated that the best biocompatible silk combination was of 5% silk fibroin and 5% Aloe vera gel in which wounds were healed in 13 days with wound contraction: 98.33 ± 0.80%. In contrast, the wound of the control group (polyfax) healed in 19 day shaving 98.5 ± 0.67% contraction. Histological analysis revealed that the wounds which were treated with silk formulations exhibited an increased growth of blood vessels, collagen fibers, and much reduced inflammation. Conclusion It can be concluded that a combination of Bombyx mori silk and Aloe vera gel is a natural biomaterial that can be utilized in wound dressings and to prepare more innovative silk based formulations for speedy recovery of chronic wounds.

Axon regeneration is an energy-demanding process that requires active mitochondrial transport. In contrast to the central nervous system (CNS), axonal mitochondrial transport in regenerating axons of the peripheral nervous system (PNS) increases within hours and sustains for weeks after injury. Yet, little is known about targeting mitochondria in nervous system repair. Here, we report the induction of sustained axon regeneration, neural activities in the superior colliculus (SC), and visual function recovery after optic nerve crush (ONC) by M1, a small molecule that promotes mitochondrial fusion and transport. We demonstrated that M1 enhanced mitochondrial dynamics in cultured neurons and accelerated in vivo axon regeneration in the PNS. Ex vivo time-lapse imaging and kymograph analysis showed that M1 greatly increased mitochondrial length, axonal mitochondrial motility, and transport velocity in peripheral axons of the sciatic nerves. Following ONC, M1 increased the number of axons regenerating through the optic chiasm into multiple subcortical areas and promoted the recovery of local field potentials in the SC after optogenetic stimulation of retinal ganglion cells, resulting in complete recovery of the pupillary light reflex, and restoration of the response to looming visual stimuli was detected. M1 increased the gene expression of mitochondrial fusion proteins and major axonal transport machinery in both the PNS and CNS neurons without inducing inflammatory responses. The knockdown of two key mitochondrial genes, Opa1 or Mfn2 , abolished the growth-promoting effects of M1 after ONC, suggesting that maintaining a highly dynamic mitochondrial population in axons is required for successful CNS axon regeneration.