Editors' ChoiceNeuroscience

Proteases, Neurotrophins, and Memory

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Science's STKE  19 Oct 2004:
Vol. 2004, Issue 255, pp. tw378
DOI: 10.1126/stke.2552004tw378

Brain-derived neurotrophic factor (BDNF)-dependent plasticity in the nervous system is thought to be essential for synaptic growth during development as well as during learning. Both tissue plasminogen activator (tPA) and BDNF have been implicated in activity-dependent plasticity, including long-term potentiation (LTP). Pang et al. (see the news story by Couzin) provide a mechanistic link between tPA and BDNF. The late phase of LTP depends on a sequence of extracellular proteolytic processes involving the proteases tPA and plasmin, and BDNF. Activation of tPA cleaves plasminogen, yielding plasmin, which in turn converts proBDNF to mature BDNF (mBDNF). Interference with any step in this sequential pathway blocks late-phase LTP, which could be rescued by reintroducing elements that occur later in the pathway.

P. T. Pang, H. K. Teng, E. Zaitsev, N. T. Woo, K. Sakata, S. Zhen, K. K. Teng, W.-H. Yung, B. L. Hempstead, B. Lu, Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science 306, 487-491 (2004). [Abstract] [Full Text]

J. Couzin, Withdrawal of Vioxx casts a shadow over COX-2 inhibitors. Science 306, 384-385 (2004). [Summary] [Full Text]

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