Effect of Transition Metals on Polysialic Acid Structure and Functions. (15th March 2016)

• Record Type: Journal Article
• Authors: Murthy, Raghavendra Vasudeva; Bharate, Priya; Gade, Madhuri; Sangabathuni, Sivakoti; Kikkeri, Raghavendra
• Is Part Of: ChemMedChem. Volume 11:Number 7(2016)
• Page Start: 667
• Page End: 673
• Publication Date: 2016-03-15
• Subjects: kinases -- neural cell differentiation -- polysialic acid -- toxicity -- transition metals; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600023
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Polysialic acid (PSA) is one of the most abundant glycopolymer present in embryonic brain, and it is known to be involved in key roles such as plasticity in the central nervous system, cell adhesion, migration and localization of neurotrophins. However, in adult brain, its expression is quite low. The exception to this is in Alzheimer′s disease (AD) brain, where significantly increased levels of polysilylated neural cell adhesion molecule (PSA‐NCAM) have been reported. Here, we confirm the role of PSA as a metal chelator, allowing it to decrease cytotoxicity caused by high levels of transition metals, commonly found in AD brain, and as a regulator of cell behavior. UV‐visible (UV‐vis) and circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), and isothermal titration calorimetry (ITC) techniques were used to investigate the assembly of PSA–metals complexes. These PSA–metal complexes exhibited less toxicity compared to free metal ions, and in particular, the PSA–Cu 2+ complex synergistically promoted neurite outgrowth in PC12 cells. Abstract : Sequestering AD : Polysialic acid, a neuronal glycopolymer, is confirmed as an effective transition metal chelator able to protect neural (PC12) cells from metal‐induced toxicity. Furthermore, the PSA–Cu 2+ complex synergistically promoted neurite outgrowth. These findings may shed light on the high levels of polysilylated neural cell adhesion molecule observed in Alzheimer′s disease brain.