Novel synthetic lipopeptides derived from Mycoplasma hyorhinis upregulate calpastatin in SH-SY5Y neuroblastoma cells and induce a neuroprotective effect against amyloid-β-peptide toxicity.

Previously, we showed that contamination of SH-SY5Y neuroblastoma cells by Mycoplasma hyorhinis strains NDMh and MCLD leads to increased levels of calpastatin (the endogenous, specific inhibitor of the Ca2+-dependent protease calpain), resulting in inhibition of calpain activation. We have found that the increased calpastatin level is promoted by the lipoprotein fraction (MhLpp) of the mycoplasmal membrane. Here, we present MhLpp-based novel synthetic lipopeptides that induce upregulation of calpastatin in SH-SY5Y neuroblastoma cells, leading to protection of the treated cells against Ca2+/amyloid-β-peptide toxicity. These lipopeptides present a new class of promising agents against calpain-induced cell toxicity.