The ?-alanyl-l-histidine dipeptide (carnosine) has been shown to act as an intracellular pH buffering molecule, Zn/Cu ion chelator, antioxidant and anticrosslinking agent. Its presence in the central nervous system is beneficial as it is able to counteract protein accumulation and proteotoxicity involved in neurodegenerative conditions, such as Alzheimer's disease (AD). Molecular studies have accomplished numerous approaches for biological and chemical interventions against amyloid disorders. Avoiding self-assembly of the A? peptide is an attractive therapeutic strategy. Here, we attempt to join notions on the structural properties of proteins in the amyloid state with published data about the carnosine direct impact on the dynamics of AD-related fibril formation. Spectroscopic techniques, as well as AFM, TEM, thermally induced unfolding analysis, and molecular dynamics have been exploited in order to assess and quantify the effect of this famed natural occurring molecule on the physical chemistry of amyloid fibril. The aim of this chapter is to review the encouraging results accomplished so far with a view to further development.
Carnosine and Alzheimer's Disease-Related Fibril Formation in Imidazole Dipeptides : Chemistry, Analysis, Function and Effects
A Aloisi;
2015
Abstract
The ?-alanyl-l-histidine dipeptide (carnosine) has been shown to act as an intracellular pH buffering molecule, Zn/Cu ion chelator, antioxidant and anticrosslinking agent. Its presence in the central nervous system is beneficial as it is able to counteract protein accumulation and proteotoxicity involved in neurodegenerative conditions, such as Alzheimer's disease (AD). Molecular studies have accomplished numerous approaches for biological and chemical interventions against amyloid disorders. Avoiding self-assembly of the A? peptide is an attractive therapeutic strategy. Here, we attempt to join notions on the structural properties of proteins in the amyloid state with published data about the carnosine direct impact on the dynamics of AD-related fibril formation. Spectroscopic techniques, as well as AFM, TEM, thermally induced unfolding analysis, and molecular dynamics have been exploited in order to assess and quantify the effect of this famed natural occurring molecule on the physical chemistry of amyloid fibril. The aim of this chapter is to review the encouraging results accomplished so far with a view to further development.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
