Abstract
Parkinson’s disease (PD) arises as neurodegenerative disorder and characterized by progressive deterioration of motor functions due to forfeiture of dopamine-releasing neurons. During PD, neurons at stake loss their functionality that results into cognition impairment and forgetfulness, commonly called as dementia. Recently, nanoparticles (NPs) have been reported for easy drug delivery through blood-brain barrier (BBB) into the central nervous system (CNS) against the conventional drug delivery systems. However, present study attempted to elucidate the α-synuclein activity, a major factor casing PD, in presence of its inhibitor cerium oxide (CeO2) nanoparticle via computational biology approach. A computational analysis was also conducted for the α-synuclein activity with biocompatible metal NPs such as GOLD NPs and SPIONs to scrutinize the efficacy and degree of inhibition induced by the CeO2 NP. The obtained results concluded that CeO2 NP fit best in the active site of α-synuclein with good contacts and interaction, and potentially inhibited the PD against L-DOPA drug selected as positive control in the designed PD biochemical pathway. Hence, CeO2 NP has been purposed as potential inhibitor of α-synuclein and can be employed as nano-drug against the PD.
Highlights
Neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Multiple sclerosis (MS), Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS) following viral infections, are multifaceted disorders occurred due to amalgamation of both genetic and environmental factors on set of aging[1,2]
(i) early diagnosis of PD is impeded due to absence of efficient bio-markers, (ii) persistent neurodegeneration during PD often results into secondary effects such as chronic inflammation and (iii) possible resistance to drugs administered into the central nervous system against PD in the brain because of blood-brain barrier (BBB), and to target specific cell types with in different CNS regions demand an efficient vectors that can carry the therapeutic agents at the target sites as summarized earlier[14]
To elucidate the activity of NPs as nanodrug on the genetically linked gene encoding most susceptible protein α-synuclein, we performed α-synuclein docking with selected NPs (CeO2, AuNP, superparamagnetic iron-oxide nanoparticles (SPIONs) NP) and L-DOPA drug molecules as standard control (Table S1)
Summary
Neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Multiple sclerosis (MS), Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS) following viral infections, are multifaceted disorders occurred due to amalgamation of both genetic and environmental factors on set of aging[1,2]. Analysis of L-DOPA drug molecule, as standard control against nano-drugs, docked with α-synuclein protein showed H-bond interaction and hydroxyl group (-OH) donor-acceptor bond with LYS10 residue and amino group (NH2) of LYS6 residue, respectively (Figs 2D and 3D).
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