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Brain & Heart

ORIGINAL RESEARCH ARTICLE
In silico investigation of lipid-based compounds

implicated in amyotrophic lateral sclerosis

Toluwase Hezekiah Fatoki * , Ibrahim Olabayode Saliu 2 ,
1
Tosin Christianah Balogun 1 , Oyeleke Ridwan Oyebiyi 1 ,
Samuel Oluwaseun Ogunleye 1 , Ayotunde Kehinde Akereja 1 ,
Abisola Eunice Iyanda 1 , Rukayat Omowumi Lukman 1 ,
Oluwaseun Oluwatosin Ogunleye 1 , Faeezah Gold Oyewo 1 ,
Enakhamiele Comfort Aigbokhaevho 1 , Yetunde Ramat Adebayo 1 ,
Blessing Odunayo Akerele 1 , Ayotunde Tope Oladimeji 1 ,
Bukunmi Oluwasayo Obata 1 , and Fatima Timileyin Yekini 1

1 Department of Biochemistry, Applied Bioinformatics Research Laboratory, Faculty of Science,
Federal University Oye-Ekiti, Oye, Ekiti State, Nigeria
2 Department of Genetics, School of Medicine, Washington University St. Louis, Missouri, United
States of America

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal, currently incurable neurodegenerative
disease that progressively affects the upper motor neurons in the brain and lower motor
neurons in the spinal cord. A significant portion of patients exhibit abnormalities in lipid
metabolism, which appear to contribute to denervation and subsequent motor neuron
degeneration. This study aimed to computationally identify lipid-based compounds
*Corresponding author: associated with ALS and elucidate their pathological and therapeutic roles to facilitate
Toluwase Hezekiah Fatoki effective ALS diagnosis and treatment. The methodologies employed encompassed
(toluwase.fatoki@fuoye.edu.ng) rational database searches, pharmacokinetic and target predictions, as well as docking
Citation: Fatoki TH, Saliu IO, and molecular dynamics simulations (MDS). The findings from the disease-to-lipids
Balogun TC, et al. In silico analysis identified 20 lipid compounds correlated with ALS, primarily categorized as
investigation of lipid-based
compounds implicated in potential inhibitors within the functional classes of vitamins, antibiotics, organic acids,
amyotrophic lateral sclerosis. and phytochemicals. Pharmacokinetic predictions revealed that only four compounds
Brain & Heart. 2024;2(3):2976. exhibited permeability across the blood–brain barrier, namely 4-hydroxynonenal,
doi: 10.36922/bh.2976 resveratrol, rotenone, and valproic acid. Docking simulations indicated the highest
Received: February 20, 2024 binding affinity for 4-hydroxynonenal with alkaline ceramidase 2 (−4.516 kcal/mol),
Accepted: April 23, 2024 resveratrol with carbonic anhydrase 6 (−7.070 kcal/mol), rotenone with cytochrome
P450 2C19 (−7.378 kcal/mol), and valproic acid with glutamate carboxypeptidase 2
Published Online: July 30, 2024 (−5.629 kcal/mol). Furthermore, MDS and molecular mechanics/generalized born
Copyright: © 2024 Author(s). surface area calculations demonstrated the stability and binding energies of the
This is an Open-Access article complexes under simulated physiological conditions. In summary, further investigation
distributed under the terms of the
Creative Commons Attribution is warranted to explore the synergistic effects of resveratrol and valproic acid in ALS,
License, permitting distribution, the mechanisms underlying 4-hydroxynonenal adduct-assisted aggregate formation
and reproduction in any medium, of certain enzymes in ALS, and the impact of prolonged human exposure to rotenone
provided the original work is
properly cited. from marine food sources (such as fish) on the development of ALS.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: Amyotrophic lateral sclerosis; Blood–brain barrier; Resveratrol; Valproic acid;
regard to jurisdictional claims in
published maps and institutional 4-Hydroxynonenal; Exposure to rotenone; Molecular targets; Docking
affiliations.

Volume 2 Issue 3 (2024) 1 doi: 10.36922/bh.2976