Influence of curcumin and rosmarinic acid on disrupting the general properties of Alpha-Synuclein oligomer: Molecular dynamics simulation

Kamelabad, Mahrokh Rezaei; Sardroodi, Jaber Jahanbin; Ebrahimzadeh, Alireza Rastkar; Ajamgard, Marzieh

doi:10.1016/j.jmgm.2021.107963

Cited by 14 publications

(8 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Curcumin may also have protective effects in MS patients [320]. This may be the case particularly due to its ability to limit pro-in lammatory cytokine secretion [321]. Table 1 shows the nutrients that can be effective for multiple sclerosis.…”

Section: Multiple Sclerosis and Nutrientsmentioning

confidence: 99%

Nutritional interventions for the prevention and treatment of neurological disorders such as anxiety, bipolar disorder, depression, epilepsy, multiple sclerosis, and schizophrenia

Madireddy¹,

Madireddy²

2022

J Neurosci Neurol Disord

View full text Add to dashboard Cite

Neurological disorders are a significant cause of mortality and disability across the world. The current aging population and population expansion have seen an increase in the prevalence of neurological and psychiatric disorders such as anxiety, bipolar disorder, depression, epilepsy, multiple sclerosis and schizophrenia. These pose a significant societal burden, especially in low - and middle-income countries. Many neurological disorders have complex mechanisms and lack definitive cures; thus, improving our understanding of them is essential. The pathophysiology of neurological disorders often includes inflammation, mitochondrial dysfunction and oxidative stress. Oxidative stress processes, especially the generation of reactive oxygen species, are key mechanisms in the development of neurological disorders. Oxidative stress refers to an imbalance between the production of reactive oxygen species and antioxidants that can counteract them. Through their impacts on the pathophysiology of neurological disorders, nutrients with anti-inflammatory, neuroprotective and antioxidative properties have been suggested to prevent or mitigate these disorders. Certain vitamins, minerals, polyphenols and flavonoids may have therapeutic effects as adjuvant treatments for neurological disorders. Diet quality is also a risk factor for some neurological and psychiatric disorders and addressing nutritional deficiencies may alleviate symptoms. Therefore, optimizing nutritional intake may represent a potential treatment or prevention strategy. This review summarizes a selection of promising nutrients for the prevention and amelioration of neurological disorders to provide a summary for scientists, clinicians and patients, which may improve understanding of the potential benefits of nutrients in the treatment of neurological disorders.

show abstract

Section: Multiple Sclerosis and Nutrientsmentioning

confidence: 99%

Nutritional interventions for the prevention and treatment of neurological disorders such as anxiety, bipolar disorder, depression, epilepsy, multiple sclerosis, and schizophrenia

Madireddy¹,

Madireddy²

2022

J Neurosci Neurol Disord

View full text Add to dashboard Cite

show abstract

“…Kamelabad et al conducted a study examining the impact of Curcumin (CUR) and Rosmarinic acid (RA) on disrupting the oligomer structure of PDB: 2N0A. In their research, they excluded all N-terminal (N-ter) and C-terminal (C-ter) residues to focus specifically on the NAC region 66 . Other studies have also utilized computational simulations, in conjunction with wet lab experiments or independently, to investigate the effects of various molecules on comparable or similar oligomers.…”

Section: Discussionmentioning

confidence: 99%

Conformational dynamics of α-synuclein and study of its intramolecular forces in the presence of selected compounds

Khatooni,

Akhtari,

Wilson

2023

Sci Rep

View full text Add to dashboard Cite

Protein misfolding and aggregation play crucial roles in amyloidogenic diseases through the self-assembly of intrinsically disordered proteins (IDPs) in type II diabetes (T2D), Alzheimer's disease (AD) and Parkinson’s disease (PD). PD is the most common neurodegenerative disorder after AD, and is associated with the loss of dopaminergic signaling, which causes motor and nonmotor signs and symptoms. Lewy bodies and Lewy neurites are common pathological hallmarks of PD that are mainly composed of aggregates of disordered α-synuclein (α-Syn). There have been many efforts to develop chemical compounds to prevent aggregation or facilitate disruption of the aggregates. Furthermore, the roles and interactions of many compounds have yet to be revealed at the atomistic level, especially their impacts on the dynamics and chain-chain interactions of the oligomers, which are of interest in this study. The conformational diversity and detailed interactions among homo-oligomer chains of α-Syn are not fully discovered; identifying these might help uncover a practical approach to developing a potent therapy. In this study, we used an in-silico investigation to address the conformational diversity of α-Syn oligomer. The roles of several point mutations in protein aggregation in PD are known; we take this further by evaluating the interaction energies and contributions of all residues in stability and residue-chain interactions. In this study, we docked chemical derivatives of three compounds with high drug-likeness properties to evaluate the roles of our ligands in the conformational dynamicity of the oligomers, with emphasis on intramolecular forces. Free energy evaluation of the modeled inter and intramolecular interactions through MD simulation shows effective interaction and binding between α-Syn and our compounds. However, we find that they do not significantly disrupt the chain-chain interactions, compared to unliganded simulation.

show abstract

“…Interestingly, a direct physical interaction between RA and αSyn has been confirmed in NMR experiments (Rao et al, 2008). More recently, Kamelabad and colleagues have proposed the structural mechanisms of RA‐mediated inhibition of αSyn oligomerization using molecular dynamics stimulation (Rezaei Kamelabad et al, 2021). Other studies have also proposed similar anti‐fibrillogenic effects of RA in α‐synucleinopathies (Lansbury & Brice, 2002; Outeiro et al, 2008; Takahashi et al, 2015).…”

Section: Neuroprotective Mechanisms Of Ramentioning

confidence: 99%

Molecular mechanisms of neuroprotective offerings by rosmarinic acid against neurodegenerative and other CNS pathologies

Ravaria

Saxena

et al. 2023

Phytotherapy Research

View full text Add to dashboard Cite

Rosmarinic acid (RA) is a natural phenolic compound present in culinary herbs of the Boraginaceae, Lamiaceae/Labiatae, and Nepetoideae families. While the medicinal applications of these plants have been known for ages, RA has only been relatively recently established as an effective ameliorative agent against various disorders including cardiac diseases, cancer, and neuropathologies. In particular, several studies have confirmed the neuroprotective potential of RA in multiple cellular and animal models, as well as in clinical studies. The neuroprotective effects mediated by RA stem from its multimodal actions on a plethora of cellular and molecular pathways; including oxidative, bioenergetic, neuroinflammatory, and synaptic signaling. In recent years, RA has garnered tremendous interest as an ideal therapeutic candidate for treating neurodegenerative diseases. This review first briefly discusses the pharmacokinetics of RA and then proceeds to detail the neuroprotective mechanisms of RA at the molecular levels. Finally, the authors focus on the ameliorative potential of RA against several central nervous system (CNS) disorders, ranging from neuropsychological stress and epilepsy to neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, Lewy body dementia, and amyotrophic lateral sclerosis.

show abstract

Influence of curcumin and rosmarinic acid on disrupting the general properties of Alpha-Synuclein oligomer: Molecular dynamics simulation

Cited by 14 publications

References 73 publications

Nutritional interventions for the prevention and treatment of neurological disorders such as anxiety, bipolar disorder, depression, epilepsy, multiple sclerosis, and schizophrenia

Nutritional interventions for the prevention and treatment of neurological disorders such as anxiety, bipolar disorder, depression, epilepsy, multiple sclerosis, and schizophrenia

Conformational dynamics of α-synuclein and study of its intramolecular forces in the presence of selected compounds

Molecular mechanisms of neuroprotective offerings by rosmarinic acid against neurodegenerative and other CNS pathologies

Contact Info

Product

Resources

About