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Mar. Drugs 2017, 15(8), 246; doi:10.3390/md15080246

The Neuroprotective Marine Compound Psammaplysene A Binds the RNA-Binding Protein HNRNPK

1
Department of Pediatrics, Division of Neurology, Research Institute, Children’s Hospital of Philadelphia, Room 814, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA
2
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
3
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
4
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
5
School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan
6
Department of Nanoparticle Translational Research, Tokyo Medical University 6-1-1, Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan
7
Children’s Hospital of Philadelphia Research Institute, Protein and Proteomics Core, Philadelphia, PA 19104, USA
*
Author to whom correspondence should be addressed.
Received: 3 July 2017 / Revised: 19 July 2017 / Accepted: 24 July 2017 / Published: 7 August 2017
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Abstract

In previous work, we characterized the strong neuroprotective properties of the marine compound Psammaplysene A (PA) in in vitro and in vivo models of neurodegeneration. Based on its strong neuroprotective activity, the current work attempts to identify the physical target of PA to gain mechanistic insight into its molecular action. Two distinct methods, used in parallel, to purify protein-binding partners of PA led to the identification of HNRNPK as a direct target of PA. Based on surface plasmon resonance, we find that the binding of PA to HNRNPK is RNA-dependent. These findings suggest a role for HNRNPK-dependent processes in neurodegeneration/neuroprotection, and warrant further study of HNRNPK in this context. View Full-Text
Keywords: Psammaplysene A; neurodegeneration; foxo; HNRNPK; RNA metabolism Psammaplysene A; neurodegeneration; foxo; HNRNPK; RNA metabolism
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MDPI and ACS Style

Boccitto, M.; Lee, N.; Sakamoto, S.; Spruce, L.A.; Handa, H.; Clardy, J.; Seeholzer, S.H.; Kalb, R.G. The Neuroprotective Marine Compound Psammaplysene A Binds the RNA-Binding Protein HNRNPK. Mar. Drugs 2017, 15, 246.

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