Ganoderic Acid A targeting leucine‐rich repeat kinase 2 involved in Parkinson's disease–A computational study

Abstract

BackgroundParkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease (AD). The exact mechanism behind PD disease is still unknown and PD is marked by symptoms like bradikynesia, tremors, walking or gait difficulties, etc. The current medication used for PD is levodopa, and researchers are trying to develop a promising drug for PD. In our study, we took Ganodema lucidium mushroom, known as “Reishi mushroom,” which has antioxidant, antiinflammatory, antihepatic properties, etc. In our study we took the most five potent Ganodema lucidium extracts, which target Leucine‐rich repeat kinase 2 (LRRK2) that is involved in onset of PD.ObjectiveThis study aims to find the most promising Ganodema lucidium targeting LRRK2 involved in PD.MethodsFirst ADMET analysis was performed for five compounds followed by molecular docking of each compound. Then, we perform molecular dynamics simulation of all five compounds and finally MMGBSA of all five compounds.ResultsBased on molecular dynamics and MMGBSA result we reach the conclusion that Ganoderic Acid A (GAA) is the most promising compound targeting LRRK2. Therefore, GAA needs further validation through in vitro and in vivo studies.

Neuroprotective Effects of Polysaccharides and Gallic Acid from Amauroderma rugosum against 6-OHDA-Induced Toxicity in SH-SY5Y Cells

“…This combined effect may arise from the preservation of mitochondrial functional integrity [ 16 ]. The molecular dynamics simulation results also indicated that ganoderic acid A has the potential to effectively target Leucine-rich repeat kinase 2 (LRRK2) [ 17 ]. LRRK2 is strongly associated with neurological illnesses, particularly PD, as certain genetic variations in this gene have been found to increase susceptibility to PD.…”

In-silico, Synthesis, Characterization, and In-vitro Studies on Benzylidene-based 2-chloroquinolin Derivatives as Free Radical Scavengers in Parkinson’s Disease

“…The overall sum between all these variables was calculated in one variable known as ΔGbind. Further, the parameters such as ΔG covalent , ΔG couloumb , and ΔG vdW were also calculated using the MM-GBSA module of the Schrodinger suite 2022 [20]. The compound JD-7 was found to have the highest binding score (− 7.94 kcal/mol) with the 4FVT, among all the designed quinoline derivatives.…”

The Biological Activity of Ganoderma lucidum on Neurodegenerative Diseases: The Interplay between Different Active Compounds and the Pathological Hallmarks

“…Ganoderic acid A (GAA) represents the most thoroughly researched among ganoderic acids derived from Ganoderma lucidum due to its effects against NDDs. For example, Ahmad et al [ 74 ] investigated the potential of GAA against PD through a computational analysis involving ADMET analysis, molecular docking, molecular dynamics simulations, and MMGBSA calculations. Focused on the leucine-rich repeat kinase 2 (LRRK2), a key protein implicated in PD, the study concluded that GAA exhibited promising therapeutic effects necessitating further in vitro and in vivo validation.…”