Anti-Parkinsonian L-Dopa can also act as anti-systemic amyloidosis—A mechanistic exploration
2017
Nusrat, Saima | Zaidi, Nida | Siddqi, Mohammad Khursheed | Zaman, Masihuz | Siddique, Ibrar Ahmed | Ajmal, Mohammad Rehan | Abdelhameed, Ali Saber | Khan, Rizwan Hasan
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±0.09μM. 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 DC50 value 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.
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