ArticleACS chemical neuroscience2026
TPEN, a Well-Known Zinc Chelator, Sequesters Attomolar-Buffered Cellular Cu(I) Through an Oxygen-Dependent Mechanism.
Arielle Nabatilan, Elena Sergeeva, M Thomas Morgan, Abigail H Wright, Larry I Benowitz, Paul A Rosenberg, Christoph J Fahrni
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In one paragraphArticle in ACS chemical neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
Arielle NabatilanSchool of Chemistry and Biochemistry and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia30332, United States.
Elena SergeevaF.M. Kirby Neurobiology Center and Departments of Neurology and Neurosurgery, Boston Children's Hospital Harvard Medical School, Boston, Massachusetts02115, United States.
M Thomas MorganSchool of Chemistry and Biochemistry and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia30332, United States.
Abigail H WrightSchool of Chemistry and Biochemistry and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia30332, United States.
Larry I BenowitzF.M. Kirby Neurobiology Center and Departments of Neurology and Neurosurgery, Boston Children's Hospital Harvard Medical School, Boston, Massachusetts02115, United States.
Paul A RosenbergF.M. Kirby Neurobiology Center and Departments of Neurology and Neurosurgery, Boston Children's Hospital Harvard Medical School, Boston, Massachusetts02115, United States.ORCID 0000-0002-5185-1118 Christoph J FahrniSchool of Chemistry and Biochemistry and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia30332, United States.ORCID 0000-0003-3731-7434 Funding
SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI POMEROY, SCOTT LOREN · 1985 to 2015
$26.2MAn interneuronal signaling network governs the fate of retinal ganglion cells after optic nerve injuryR01EY027881 · NEI · BOSTON CHILDREN'S HOSPITAL · PI ROSENBERG, PAUL ALLEN · 2018 to 2022
$3.5MZinc is a critical regulator of cell death and axon regeneration after CNS injuryR01EY024481 · NEI · BOSTON CHILDREN'S HOSPITAL · PI BENOWITZ, LARRY IRA, ROSENBERG, PAUL ALLEN · 2015 to 2019
$2.8MMolecular Tools to Illuminate Copper Transport and HomeostasisR35GM136404 · NIGMS · GEORGIA INSTITUTE OF TECHNOLOGY · PI FAHRNI, CHRISTOPH J · 2020 to 2024
$2.2MNEI NIH HHS R01 EY024481NEI NIH HHS R01 EY027881NICHD NIH HHS P30 HD018655NIGMS NIH HHS R35 GM136404NIH HHS EY024481NIH HHS EY027881NIH HHS GM136404NIH HHS P30 HD018655
6 · The paper itselfAbstract
The metal ion chelator TPEN is widely used to study the role of mobile zinc in biology; however, its high affinity for other metal ions raises questions about the specificity when interpreting biological effects of TPEN. Using the Cu(I)-selective chelator PSP-2, we found that the chelation of copper, and not zinc, likely stimulates axon regeneration after optic nerve injury, thus challenging the previous viewpoint that dysregulation of mobile zinc contributes to regenerative failure upon optic nerve damage. Spectroscopic and electrochemical measurements revealed that TPEN sequesters subattomolar buffered Cu(I) through a novel redox-trapping mechanism, which was corroborated by fluorescence imaging studies with a Cu(I)-selective probe in live cells. These findings highlight the ambiguity of TPEN-induced biological effects and identify PSP-2 as a versatile tool for dissecting the role of copper in biological processes.
Indexed as
Chelating AgentsCopperEthylenediaminesOxygenZincAnimalsOptic Nerve InjuriesChelating AgentsCopperEthylenediaminesN,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamineOxygenZincaxon regenerationcopperoptic nerve injuryPSP-2redox trappingTPENzinc
Identifiers
PMID42615641
PMCPMC13495674
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