Harnessing cAMP signaling in musculoskeletal regenerative engineering

Ifegwu, Okechukwu Clinton; Awale, Guleid; Rajpura, Komal; Lo, Kevin W.‐H.; Laurencin, Cato T.

doi:10.1016/j.drudis.2017.03.008

Cited by 10 publications

(1 citation statement)

References 174 publications

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“…It has been seen that in vivo injection of dibutyryl cAMP (db-cAMP) in dorsal root ganglion (DRG) leads to potentiated regeneration of central axons even in the presence of MAIs, thus mimicking conditioning lesions [ 20 ]. Another study on zebrafish exhibits an increase in the growth of neurons after induction of exogenous cAMP [ 21 ]. Many studies show that cAMP signalling stimulates multiple downstream pathways that drive neurite outgrowth after damage [ 22 ].…”

Section: Molecular Pathways and Therapeutic Targetsmentioning

confidence: 99%

Axonal Regeneration: Underlying Molecular Mechanisms and Potential Therapeutic Targets

et al. 2022

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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.

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Section: Molecular Pathways and Therapeutic Targetsmentioning

confidence: 99%