Carnosine promotes GAPDH dimer formation: proposed role in preventing neurodegeneration

Carnosine (beta‐alanyl‐L‐histidine) is an endogenous dipeptide found in millimolar concentrations in the brain. It is neuroprotective, presumably due to its antioxidant and anti‐glycation properties. More recently, carnosine was shown to have an anti‐aggregation effect. Interestingly, beta‐alanine, a component of carnosine, stabilizes protein structure. We were interested in examining the effects of carnosine on the stability and oligomeric state of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) structure. GAPDH was denatured using guanidine‐HCl in the presence and absence of carnosine. We observed that guanidine‐HCl caused a biphasic response in the absorbance spectra, suggesting that the denaturation of GAPDH involves changes in quaternary structure prior to loss of tertiary conformation. Carnosine promoted the first phase of denaturation, suggesting that carnosine promotes the dissociation of the tetramer. Additionally, carnosine effected the oligomeric properties of GAPDH, promoting dimer and decamer formation in favor of the control tetrameric arrangement. Though GAPDH participates in glycolysis, GAPDH plays a role in neurodegeneration through induction of apoptosis and amyloid fibril formation. We propose that carnosine's association with GAPDH may ameliorate the protein's involvement in neuronal degenerative events.