An insight into the inhibition of fibrillation process verses disaggregation of preformed fibrils of bovine serum albumin by isoprenaline hydrochloride.

This study is based on the analysis of the recent trend of medication in neurodegenerative diseases. Due to the asymptomatic nature of the diseases, medication delays. Therefore, mechanism of medication assists in removal of the symptoms. Therefore, in order to find out remedy for complete prevention of the disease we have considered "inhibition verses disaggregation" study. Various biophysical techniques such as turbidity measurement (TM), Thioflavin T (ThT) binding assays, circular dichroism (CD), transmission electron microscopy (TEM) etc. has been performed. Isoprenaline hydrochloride (ISO) was a good candidate for inhibition and disaggregation of preformed fibrils of BSA. Therefore, it is concluded that inhibition of fibrillation process was more momentous, effective procedure in restricting the aggregation by stabilizing the native conformation of BSA than the removal of preformed amyloid fibrils under in vitro condition. Forwarding ahead, to understand the efficiency of the two processes under in vivo condition, this study can be applied on animal models so that we can look forward on human beings as well for the development of vaccines. This study is concerned about the applied aspect of research in future so that we can hope for prevention of the disease instead of only removal of the symptoms.

A multiparametric analysis of the synergistic impact of anti-Parkinson's drugs on the fibrillation of human serum albumin.

Protein aggregation have been associated with several human neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases. There are several small molecules that can reduce aggregation of proteins. The present study aimed to test the hypothesis that the application of more than one inhibitor either simultaneously or consecutively may result in more efficient inhibition of protein aggregation. To this end, the anti-amyloidogenic behaviour of benserazide hydrochloride (BH) and levodopa (LD) individually and in combination (BH + LD) was investigated using various biophysical, microscopic, and computational techniques. BH, LD, and BH + LD treatments showed inhibitory effects on protein aggregation and had the ability to minimise the amyloid-induced cytotoxicity in human neuroblastoma cell line (SH-SY5Y). The two drugs in combination showed synergism (combination index, CI < 1) between them. These drugs also destabilised the preformed fibrils of human serum albumin (HSA). Our studies consistently showed that the BH + LD treatment showed highest efficacy towards inhibition and disaggregation of amyloid fibrils in comparison to treatment with BH and LD individually. Therefore, application of drugs in combination against fibrillogenesis may represent a new route for development of means for prevention or delaying of the aggregation-related diseases.

Unraveling Comparative Anti-Amyloidogenic Behavior of Pyrazinamide and D-Cycloserine: A Mechanistic Biophysical Insight.

Amyloid fibril formation by proteins leads to variety of degenerative disorders called amyloidosis. While these disorders are topic of extensive research, effective treatments are still unavailable. Thus in present study, two anti-tuberculosis drugs, i.e., pyrazinamide (PYZ) and D-cycloserine (DCS), also known for treatment for Alzheimer's dementia, were checked for the anti-aggregation and anti-amyloidogenic ability on Aß-42 peptide and hen egg white lysozyme. Results demonstrated that both drugs inhibit the heat induced aggregation; however, PYZ was more potent and decelerated the nucleation phase as observed from various spectroscopic and microscopic techniques. Furthermore, pre-formed amyloid fibrils incubated with these drugs also increased the PC12/SH-SY5Y cell viability as compare to the amyloid fibrils alone; however, the increase was more pronounced for PYZ as confirmed by MTT assay. Additionally, molecular docking study suggested that the greater inhibitory potential of PYZ as compare to DCS may be due to strong binding affinity and more occupancy of hydrophobic patches of HEWL, which is known to form the core of the protein fibrils.