Effect of Ovocystatin on Amyloid β 1-42 Aggregation—In Vitro Studies

Abstract

Amyloid β peptides (Aβ) aggregating in the brain have a potential neurotoxic effect and are believed to be a major cause of Alzheimer’s disease (AD) development. Thus, inhibiting amyloid polypeptide aggregation seems to be a promising approach to the therapy and prevention of this neurodegenerative disease. The research presented here is directed at the determination of the inhibitory activity of ovocystatin, the cysteine protease inhibitor isolated from egg white, on Aβ42 fibril genesis in vitro. Thioflavin-T (ThT) assays, which determine the degree of aggregation of amyloid peptides based on fluorescence measurement, circular dichroism spectroscopy (CD), and transmission electron microscopy (TEM) have been used to assess the inhibition of amyloid fibril formation by ovocystatin. Amyloid beta 42 oligomer toxicity was measured using the MTT test. The results have shown that ovocystatin possesses Aβ42 anti-aggregation activity and inhibits Aβ42 oligomer toxicity in PC12 cells. The results of this work may help in the development of potential substances able to prevent or delay the process of beta-amyloid aggregation—one of the main reasons for Alzheimer’s disease.

Innovative Cyanine-Based Fluorescent Dye for Targeted Mitochondrial Imaging and Its Utility in Whole-Brain Visualization

“…Aβ peptides have been identified as the cause of dendritic degeneration and loss of synapses, which ultimately leads to neuronal death in the rat hippocampus . Additionally, in vitro studies using cells from PC12 cells (rat pheochromocytoma , and SH-SY5Y cells) , (human neuroblastoma) have demonstrated that extracellular fibrillar aggregates of Aβ peptides are neurotoxic. However, these cells are unsuitable for neurodegenerative disease research due to their instability and inability to create a diverse population of neurons.…”

Targeting and Imaging Mitochondria with a Novel Cyanine-based Fluorescent Dye and Its Application to Whole Brain Imaging

“…Aβ peptides have been identified as the cause of dendritic degeneration and loss of synapses, which ultimately leads to neuronal death in the rat hippocampus. 12 Additionally, in vitro studies using cells from PC12 cells (rat pheochromocytoma 14,15 and SH-SY5Y cells 16,17 (human neuroblastoma) have demonstrated that extracellular fibrillar aggregates of Aβ peptides are neurotoxic. However, these cells are unsuitable for neurodegenerative disease research due to their instability and inability to create a diverse population of neurons.…”

Cystatins: unravelling the biological implications for neuroprotection

“…With limited evidence for ovocystatin passage through the blood-brain barrier to the brain compartment, it is also possible that the observed effects were exerted peripherally and indirectly led to the changes in the brain tissue. In another study it was found that the use of ovocystatin in vitro led to reduced aggregation of 1-42 β-amyloid and in turn significantly decreased its toxicity in the PC12 cell line [ 115 ].…”