The signaling enzyme Phospholipase D (PLD) has been implicated in numerous cell biological processes, including Ras activation, cell spreading, stress fiber formation, chemotaxis, and vesicular trafficking during neurotransmitter and hormonal release. These observations have been mostly obtained from cell culture experiments using a primary alcohol to inhibit PLD activity or by modulating endogenous expression levels of the PLD1 and PLD2 isoforms. Since modulating PLD levels can have non-specific long-term effects and alcohols have been described to cause PLD-independent deleterious effects, the identification of potent specific small molecule PLD inhibitors is an important advance for the field. In this review, I will highlight the recent identification and characterization of chemical PLD inhibitors and describe their potential therapeutic interest in the treatment of human brain diseases/disorders and cancer metastasis.
Keywords: Phospholipase D, inhibitor, cancer, immunity, cognition
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