To confirm the impact of thrombin on the NMJ, the researchers looked at a mouse model where thrombin was absent or nonfunctioning, and found that these mice experienced less nerve axon degeneration. These results affirm that thrombin plays a role in nerve axon degeneration.
“This study provides an understanding of the genetic and molecular pathways that alter synapse development and maintenance,” says Lee, holder of the Helen McLoraine Chair in Molecular Neurobiology. “The next step is to understand the mechanism of how thrombin and other enzymes destroy the synapse—with the eventual goal of creating an intervention for diseases—such as ALS, MS and Alzheimer’s—where thrombin accumulation or dysregulation has been implicated.”
Other authors included: Bertha Dominguez and Fred de Winter of Salk; Gene W. Yeo, Patrick Liu, Balaji Sundararaman, Thomas Stark and Anthony Vu of the University of California San Diego; Jay L. Degen of the Cincinnati Children’s Hospital Research Foundation; and Weichun Lin of the University of Texas Southwestern Medical Center.
The work was funded by grants from the National Institutes of Health (GM103554, NS107922, NS055028, NS075449, HG004659, HL096126, NS044420, NS060833, AG0476669, OD023076, MH114831, AG062232), The Clayton Foundation, the Schlink Foundation, the Gemcon Family Foundation, the Brown Foundation, and the Freeburg Foundation.
About the Salk Institute for Biological Studies:
Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology, plant biology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin.