Open AccessInhibition of GCK-IV kinases dissociates cell death and axon regeneration in CNS neurons
Author(s) -
Amit K. Patel,
Risa Broyer,
Cassidy D. Lee,
Tianlun Lu,
Mikaela Louie,
Anna La Torre,
Hassan Al-Ali,
Mai Vu,
Kathryn Mitchell,
Karl Wahlin,
Cynthia Berlinicke,
Vinod Jaskula-Ranga,
Yang Hu,
Xin Duan,
Santiago Vilar,
John L. Bixby,
Robert N. Weinreb,
Vance Lemmon,
Donald J. Zack,
Derek S. Welsbie
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2004683117
Subject(s) - biology , kinase , microbiology and biotechnology , neuroprotection , neurite , axon , regeneration (biology) , programmed cell death , neuroscience , genetics , apoptosis , in vitro
Significance Axonal injury plays a major role in many neurodegenerative diseases. The dual leucine zipper kinase (DLK) signaling pathway is a key regulator of axonal injury-induced neuronal cell death; however, DLK also has an important role in promoting axonal outgrowth. Therefore, inhibiting DLK as a therapeutic approach for neurodegenerative diseases is limited to a neuroprotective outcome without axon regeneration, prohibiting restoration of function. In fact, there are currently no strategies that provide long-term neuroprotection and axonal regeneration after injury. Here, we identified the germinal cell kinase four (GCK-IV) family of kinases as targets to maximize neuroprotection while promoting axon regeneration, making it an attractive therapeutic approach for a subset of neurodegenerative diseases.