Beta-lactam antibiotics are multipotent agents to combat neurological diseases.

Recently, Rothstein et al. reported that beta-lactam antibiotics, including penicillin and ceftriaxone, are potential therapeutic drugs to treat some neurological disorders, e.g., amyotrophic lateral sclerosis (ALS), by modulating the expression of glutamate transporter GLT1 via gene activation. However, considering the facts that: (i) many neurological diseases (including ALS) are associated with transition metal ions and redox stress, and ALS can be efficiently prevented by metal chelators, e.g., diethyl-dithiocarbamate (DDC); (ii) beta-lactam antibiotics have long been known as metal chelators, we argue that the beneficial effect of beta-lactam antibiotics on ALS likely involves Cu(II)-attenuating ability. This is partially supported by our theoretical calculations.