Title
Anti-Parkinsonian L-Dopa can also act as anti-systemic amyloidosis—A mechanistic exploration
Author
Saima Nusrat, Nida Zaidi, Mohammad Khursheed Siddiqi, Masihuz Zaman, Ibrar Ahmed Siddique, Mohammad Rehan Ajmal, Ali Saber Abdelhameed, Rizwan Hasan Khan
Year
2017
Journal
International Journal of Biological Macromolecules
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 IC50 value of L-Dopa is calculated to be 63.0 ± 0.09 μM. 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 ± 0.063 μM. Hence, L-Dopa and related compounds can act as effective inhibitors in the therapeutic development to combat systemic amyloidosis.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Aggregation, Biochemistry