title: Anti-Parkinsonian L-Dopa can also act as anti-systemic amyloidosis-A mechanistic exploration.
abstract: In spite of the fact that amyloid related neurodegenerative illnesses and non-neuropathic systemic amyloidosis have allured the research endeavors, as no cure has been announced yet apart from symptomatic treatment. Therapeutic agents which can reduce or disaggregate those toxic oligomers and fibrillar species have been studied with more compounds are on their way. The current research work describes comprehensive biophysical, computational and microscopic studies which reveal that L-3, 4-dihydroxyphenylalanine (L-Dopa) have indisputable efficacy to hinder the heat induced amyloid fibrillation of the human lysozyme (HL) and also preserve the fibril disaggregating potential. The IC50value of L-Dopa is calculated to be 63.0±0.09μM. L-Dopa intervenes in the process of amyloid fibrillogenesis through hydrophobic interaction and hydrogen bond formation with the amino acid residues found in the amyloid fibril forming prone region of HL as clarified by molecular simulation data. L-Dopa also disaggregates the mature amyloid fibrils into some unorganized species and the DC50value was estimated to be 19.95±0.063μM. Hence, L-Dopa and related compounds can act as effective inhibitors in the therapeutic development to combat systemic amyloidosis.
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Saima
authors.initials: S
authors.lastname: Nusrat
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Nida
authors.initials: N
authors.lastname: Zaidi
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Mohammad Khursheed
authors.initials: MK
authors.lastname: Siddiqi
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Masihuz
authors.initials: M
authors.lastname: Zaman
authors.affiliation: Molecular Science Lab, National Institute of Immunology, New Delhi 110067, India.
authors.forename: Ibrar Ahmed
authors.initials: IA
authors.lastname: Siddique
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Mohammad Rehan
authors.initials: MR
authors.lastname: Ajmal
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Ali Saber
authors.initials: AS
authors.lastname: Abdelhameed
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India. Electronic address: rizwanhkhan@hotmail.com.
authors.forename: Rizwan Hasan
authors.initials: RH
authors.lastname: Khan
mesh_terms: D000686:Amyloidosis / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D007980:Levodopa / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D062105:Molecular Docking Simulation; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects
chemical_list: D007980:Levodopa; D009113:Muramidase
keywords: Amyloids; Disaggregation; Human lysozyme; IC(50); Molecular docking