A novel neuroprotective mechanism for lithium that prevents association of the p75NTR-sortilin receptor complex and attenuates proNGF-induced neuronal death in vitro and in vivo

Shayri G. Greenwood, Laura Montroull, Marta Volosin, Helen E. Scharfman, Kenneth K. Teng, Matthew Light, Risa Torkin, Fredrick Maxfield, Barbara L. Hempstead, Wilma Friedman

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Neurotrophins play critical roles in the survival, maintenance and death of neurons. In particular, proneurotrophins have been shown to mediate cell death following brain injury induced by status epilepticus (SE) in rats. Previous studies have shown that pilocarpine-induced seizures lead to increased levels of proNGF, which binds to the p75NTR-sortilin receptor complex to elicit apoptosis. A screen to identify compounds that block proNGF binding and uptake into cells expressing p75 and sortilin identified lithium citrate as a potential inhibitor of proNGF and p75NTR-mediated cell death. In this study, we demonstrate that low, submicromolar doses of lithium citrate effectively inhibited proNGF-induced cell death in cultured neurons and protected hippocampal neurons following pilocarpine-induced SE in vivo. We analyzed specific mechanisms by which lithium citrate afforded neuroprotection and determined that lithium citrate prevented the association and internalization of the p75NTR-sortilin receptor complex. Our results demonstrate a novel mechanism by which low-dose treatments of lithium citrate are effective in attenuating p75NTR-mediated cell death in vitro and in vivo.

Original languageEnglish (US)
Article numbere0257-17.2017
JournaleNeuro
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Lithium
Cell Death
Pilocarpine
Status Epilepticus
Neurons
Nerve Growth Factors
Brain Injuries
Seizures
Maintenance
lithium citrate
sortilin
In Vitro Techniques
Apoptosis

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • Apoptosis
  • Neuroprotection
  • Neurotrophins
  • P75
  • ProNGF
  • Seizures

Cite this

Greenwood, Shayri G. ; Montroull, Laura ; Volosin, Marta ; Scharfman, Helen E. ; Teng, Kenneth K. ; Light, Matthew ; Torkin, Risa ; Maxfield, Fredrick ; Hempstead, Barbara L. ; Friedman, Wilma. / A novel neuroprotective mechanism for lithium that prevents association of the p75NTR-sortilin receptor complex and attenuates proNGF-induced neuronal death in vitro and in vivo. In: eNeuro. 2018 ; Vol. 5, No. 1.
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A novel neuroprotective mechanism for lithium that prevents association of the p75NTR-sortilin receptor complex and attenuates proNGF-induced neuronal death in vitro and in vivo. / Greenwood, Shayri G.; Montroull, Laura; Volosin, Marta; Scharfman, Helen E.; Teng, Kenneth K.; Light, Matthew; Torkin, Risa; Maxfield, Fredrick; Hempstead, Barbara L.; Friedman, Wilma.

In: eNeuro, Vol. 5, No. 1, e0257-17.2017, 01.01.2018.

Research output: Contribution to journalArticle

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AU - Greenwood, Shayri G.

AU - Montroull, Laura

AU - Volosin, Marta

AU - Scharfman, Helen E.

AU - Teng, Kenneth K.

AU - Light, Matthew

AU - Torkin, Risa

AU - Maxfield, Fredrick

AU - Hempstead, Barbara L.

AU - Friedman, Wilma

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