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

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

  • Biochim Biophys Acta Proteins Proteom. 2019 Mar;1867(3):275-285. doi: 10.1016/j.bbapap.2018.10.003.
Tajalli Ilm Chandel 1,  Nida Zaidi 1,  Masihuz Zaman 1,  Ishrat Jahan 2,  Aiman Masroor 1,  Ibrar Ahmad Siddique 3,  Shahid M Nayeem 2,  Maroof Ali 4,  Vladimir N Uversky 5,  Rizwan Hasan Khan 6
Affiliations

Affiliations

  • 1 Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, U.P., India.
  • 2 Chemistry Department, Aligarh Muslim University, Aligarh, U.P., India.
  • 3 Molecular Science Lab, National Institute of Immunology, New Delhi.
  • 4 Moradabad Institutes of Technology, Moradabad, U.P., India.
  • 5 Protein Research Group, Institute for Biological Instrumentation of the Russian Academy of Sciences, Institutskaya Str., 7, Pushchino, Moscow Region 142290, Russia; Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah, Saudi Arabia; Department of Molecular Medicine, USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
  • 6 Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, U.P., India. Electronic address: [email protected].
PMID: 30312771 DOI: 10.1016/j.bbapap.2018.10.003
Abstract

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.

Keywords

Amyloid fibrils; Anti-amyloidogenic agent; Cytotoxicity; Fibrillation; Human serum albumin; Inhibition.

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