β-Lactams as Neuroprotective Agents

Although, β-lactams have historically been viewed as a class of antimicrobials, in the last few decades their role as inhibitors of bacterial enzymes has been expanded. Their inhibitory activity is based on their ability to acylate enzymes, majority of which have serine as nucleophile in the active site. In addition to being inhibitors of bacterial enzymes, β-lactams also inhibit viral and mammalian serine enzymes. Recently, a blinded screening of 1,040 FDA approved drugs and nutritional compounds, has demonstrated an additional utility both in vitro and in vivo of β-lactam antibiotics (penicillins and cephalosporins) as protectors against neuroexcitotoxicity. This neuroprotection is associated with increases in the glial-associated reuptake protein, GLT1, suggesting that β-lactam's neuroprotective effects may be mediated by an increase in glutamate removal from the synapse. The focus of this review is on the evaluation of the potential of β-lactam antibiotics as neuroprotective agents.