title: Calcium-dependent proteasome activation is required for axonal neurofilament degradation.
abstract: Even though many studies have identified roles of proteasomes in axonal degeneration, the molecular mechanisms by which axonal injury regulates proteasome activity are still unclear. In the present study, we found evidence indicating that extracellular calcium influx is an upstream regulator of proteasome activity during axonal degeneration in injured peripheral nerves. In degenerating axons, the increase in proteasome activity and the degradation of ubiquitinated proteins were significantly suppressed by extracellular calcium chelation. In addition, electron microscopic findings revealed selective inhibition of neurofilament degradation, but not microtubule depolymerization or mitochondrial swelling, by the inhibition of calpain and proteasomes. Taken together, our findings suggest that calcium increase and subsequent proteasome activation are an essential initiator of neurofilament degradation in Wallerian degeneration.
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan, South Korea.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan, South Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Jang
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan, South Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Shin
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan, South Korea.
authors.forename: Duk Joon
authors.initials: DJ
authors.lastname: Suh
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan, South Korea.
authors.forename: Hwan Tae
authors.initials: HT
authors.lastname: Park
keywords: axon; axon degeneration; calcium; calpain; microtubule depolymerization; mitochondria; neural regeneration; neurofilament degradation; neuroregeneration; peripheral nerve injury; sciatic nerve