Browsing by Author "Narayanasamy, Arul"

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Assessment of tRNAThr and tRNAGln Variants and Mitochondrial Functionality in Parkinson�s Disease (PD) Patients of Tamil Nadu Population
(Springer, 2023-10-17T00:00:00) Venkatesan, Dhivya; Iyer, Mahalaxmi; Raj, Neethu; Gopalakrishnan, Abilash Valsala; Narayanasamy, Arul; Kumar, Nachimuthu Senthil; Vellingiri, Balachandar
Parkinson�s disease (PD) is speculated with genetic and environmental factors. At molecular level, the mitochondrial impact is stated to be one of the causative reasons for PD. In this study, we investigated the mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels along with mitochondrial tRNA alterations among three age categories of PD. By determining the genetic and organellar functionality using molecular techniques, the ROS levels were reported to be high with decreased MMP and ATP in the late-onset age group than in other two age categories. Likewise, the tRNA significancy in tRNAThr and tRNAGln was noticed with C4335T and G15927A mutations in late-onset and early-onset PD groups respectively. Therefore, from the findings, ageing has shown a disruption in tRNA metabolism leading to critical functioning of ATP synthesis and MMP, causing oxidative stress in PD patients. These physiological outcomes show that ageing has a keen role in the divergence of mitochondrial function, thereby proving a correlation with ageing and maintenance of mitochondrial homeostasis in PD. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Concurrent Assessment of Oxidative Stress and MT-ATP6 Gene Profiling to Facilitate Diagnosis of Autism Spectrum Disorder (ASD) in Tamil Nadu Population
(Springer, 2023-03-27T00:00:00) Vellingiri, Balachandar; Venkatesan, Dhivya; Iyer, Mahalaxmi; Mohan, Gomathi; Krishnan, Padmavathi; Sai Krishna, Krothapalli; Sangeetha, R.; Narayanasamy, Arul; Gopalakrishnan, Abilash Valsala; Kumar, Nachimuthu Senthil; Subramaniam, Mohana Devi
Autism spectrum disorder (ASD) is a neurodevelopmental disability that causes social impairment, debilitated verbal or nonverbal conversation, and restricted/repeated behavior. Recent research reveals that mitochondrial dysfunction and oxidative stress might play a pivotal role in ASD condition. The goal of this case�control study was to investigate oxidative stress and related alterations in ASD patients. In addition, the impact of mitochondrial DNA (mtDNA) mutations, particularly MT-ATP6, and its link with oxidative stress in ASD was studied. We found that ASD patient�s plasma had lower superoxide dismutase (SOD) and higher catalase (CAT) activity, resulting in lower SOD/CAT ratio. MT-ATP6 mutation analysis revealed that four variations, 8865 G>A, 8684 C>T, 8697 G>A, and 8836 A>G, have a frequency of more than 10% with missense and synonymous (silent) mutations. It was observed that abnormalities in mitochondrial complexes (I, III, V) are more common in ASD, and it may have resulted in MT-ATP6 changes or vice versa. In conclusion, our findings authenticate that oxidative stress and genetics both have an equal and potential role behind ASD and we recommend to conduct more such concurrent research to understand their unique mechanism for better diagnosis and therapeutic for ASD. Graphical Abstract: [Figure not available: see fulltext.] � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
The creation of selenium nanoparticles decorated with troxerutin and their ability to adapt to the tumour microenvironment have therapeutic implications for triple-negative breast cancer
(Royal Society of Chemistry, 2023-02-09T00:00:00) Saranya, Thiruvenkataswamy; Kavithaa, Krishnamoorthy; Paulpandi, Manickam; Ramya, Sennimalai; Winster, Sureshbabu Harysh; Mani, Geetha; Dhayalan, Sangeetha; Balachandar, Vellingiri; Narayanasamy, Arul
Despite advancements in treatment, managing aggressive types of breast cancer, particularly Triple Negative Breast Cancer (TNBC), remains a daunting task. Newer chemotherapeutics enhance the multidrug resistance in cancer cells, making them untreatable. The current research work was framed to develop a novel therapeutic target by utilizing the flavanol, troxerutin (TXN) as a drug of interest to target TNBC. And also, to increase the efficiency of the drug at the target site, a nanocarrier called selenium nanoparticles (SeNPs) has been exploited. Thus, the anticancer efficacy of TXN and Se-TXN against TNBC (in vitro and in vivo) has been compared and analysed in the present study. Se-TXN was synthesized by a precipitation approach and characterized by diverse analytical techniques, which confirmed the successful loading of TXN on the SeNPs. The inhibitory concentration (IC50) of Se-TXN was determined to be 6.5 � 0.5 ?g mL?1 according to the in vitro data. Even at lower concentrations, the existence of apoptotic bodies shows that Se-TXN is effective against TNBC. Additionally, the Se-TXN expression study shows that the activation of the caspase cascade pathway, which results in apoptosis, occurs from the downregulation of anti-apoptotic proteins and genes and the upregulation of pro-apoptotic proteins and genes. And the in vivo investigations like histopathology, hematology and biochemical parameters revealed that the Se-TXN had significantly lowered the tumour volume of treated Balb/C mice without having any significant systemic toxicity when compared to other treatment groups. Altogether, our data suggests the efficacy of Se-TXN nanoconjugates as an effective management therapy for treating TNBC. � 2023 The Royal Society of Chemistry.
miRNA in Parkinson's disease:�From pathogenesis to theranostic approaches
(John Wiley and Sons Inc, 2022-12-11T00:00:00) Elangovan, Ajay; Venkatesan, Dhivya; Selvaraj, Priyanka; Pasha, Md. Younus; Babu, Harysh Winster Suresh; Iyer, Mahalaxmi; Narayanasamy, Arul; Subramaniam, Mohana Devi; Valsala Gopalakrishnan, Abilash; Kumar, Nachimuthu Senthil; Vellingiri, Balachandar
Parkinson's disease (PD) is an age associated neurological disorder which is specified by cardinal motor symptoms such as tremor, stiffness, bradykinesia, postural instability, and non-motor symptoms. Dopaminergic neurons degradation in substantia nigra region and aggregation of ?Syn are the classic signs of molecular defects noticed in PD pathogenesis. The discovery of microRNAs (miRNA) predicted to have a pivotal part in various processes regarding regularizing the cellular functions. Studies on dysregulation of miRNA in PD pathogenesis has recently gained the concern where our review unravels the role of miRNA expression in PD and its necessity in clinical validation for therapeutic development in PD. Here, we discussed how miRNA associated with ageing process in PD through molecular mechanistic approach of miRNAs on sirtuins, tumor necrosis factor-alpha and interleukin-6, dopamine loss, oxidative stress and autophagic dysregulation. Further we have also conferred the expression of miRNAs affected by SNCA gene expression, neuronal differentiation and its therapeutic potential with PD. In conclusion, we suggest more rigorous studies should be conducted on understanding the mechanisms and functions of miRNA in PD which will eventually lead to discovery of novel and promising therapeutics for PD. � 2022 Wiley Periodicals LLC.
Plausible Role of Mitochondrial DNA Copy Number in Neurodegeneration�a Need for Therapeutic Approach in Parkinson�s Disease (PD)
(Springer, 2023-07-31T00:00:00) Venkatesan, Dhivya; Iyer, Mahalaxmi; Narayanasamy, Arul; Gopalakrishnan, Abilash Valsala; Vellingiri, Balachandar
Parkinson�s disease (PD) is an advancing age-associated progressive brain disorder which has various diverse factors, among them mitochondrial dysfunction involves in dopaminergic (DA) degeneration. Aging causes a rise in mitochondrial abnormalities which leads to structural and functional modifications in neuronal activity and cell death in PD. This ends in deterioration of mitochondrial function, mitochondrial alterations, mitochondrial DNA copy number (mtDNA CN) and oxidative phosphorylation (OXPHOS) capacity. mtDNA levels or mtDNA CN in PD have reported that mtDNA depletion would be a predisposing factor in PD pathogenesis. To maintain the mtDNA levels, therapeutic approaches have been focused on mitochondrial biogenesis in PD. The depletion of mtDNA levels in PD can be influenced by autophagic dysregulation, apoptosis, neuroinflammation, oxidative stress, sirtuins, and calcium homeostasis. The current review describes the regulation of mtDNA levels and discusses the plausible molecular pathways in mtDNA CN depletion in PD pathogenesis. We conclude by suggesting further research on mtDNA depletion which might show a promising effect in predicting and diagnosing PD. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
A review of chromium (Cr) epigenetic toxicity and health hazards
(Elsevier B.V., 2023-04-17T00:00:00) Iyer, Mahalaxmi; Anand, Uttpal; Thiruvenkataswamy, Saranya; Babu, Harysh Winster Suresh; Narayanasamy, Arul; Prajapati, Vijay Kumar; Tiwari, Chandan Kumar; Gopalakrishnan, Abilash Valsala; Bontempi, Elza; Sonne, Christian; Barcel�, Dami�; Vellingiri, Balachandar
Carcinogenic metals affect a variety of cellular processes, causing oxidative stress and cancer. The widespread distribution of these metals caused by industrial, residential, agricultural, medical, and technical activities raises concern for adverse environmental and human health effects. Of these metals, chromium (Cr) and its derivatives, including Cr(VI)-induced, are of a public health concern as they cause DNA epigenetic alterations resulting in heritable changes in gene expression. Here, we review and discuss the role of Cr(VI) in epigenetic changes, including DNA methylation, histone modifications, micro-RNA changes, biomarkers of exposure and toxicity, and highlight prevention and intervention strategies to protect susceptible populations from exposure and adverse occupational health effects. Cr(VI) is a ubiquitous toxin linked to cardiovascular, developmental, neurological, and endocrine diseases as well as immunologic disorders and a high number of cancer types in humans following inhalation and skin contact. Cr alters DNA methylation levels as well as global and gene-specific histone posttranslational modifications, emphasizing the importance of considering epigenetics as a possible mechanism underlying Cr(VI) toxicity and cell-transforming ability. Our review shows that determining the levels of Cr(VI) in occupational workers is a crucial first step in shielding health problems, including cancer and other disorders. More clinical and preventative measures are therefore needed to better understand the toxicity and safeguard employees against cancer. � 2023
Role of Telomeres and Telomerase in Parkinson's Disease�A New Theranostics?
(John Wiley and Sons Inc, 2023-08-21T00:00:00) Vellingiri, Balachandar; Balasubramani, Kiruthika; Iyer, Mahalaxmi; Raj, Neethu; Elangovan, Ajay; Song, Kwonwoo; Yeo, Han-Cheol; Jayakumar, Namitha; Kinoshita, Masako; Thangarasu, Ravimanickam; Narayanasamy, Arul; Dayem, Ahmed Abdal; Prajapati, Vijay Kumar; Gopalakrishnan, Abilash Valsala; Cho, Ssang-Goo
Parkinson's disease (PD) is a complex condition that is significantly influenced by oxidative stress and inflammation. It is also suggested that telomere shortening (TS) is regulated by oxidative stress which leads to various diseases including age-related neurodegenerative diseases like PD. Thus, it is anticipated that PD would result in TS of peripheral blood mononuclear cells (PBMCs). Telomeres protect the ends of eukaryotic chromosomes preserving them against fusion and destruction. The TS is a normal process because DNA polymerase is unable to replicate the linear ends of the DNA due to end replication complications and telomerase activity in various cell types counteracts this process. PD is usually observed in the aged population and progresses over time therefore, disparities among telomere length in PBMCs of PD patients are recorded and it is still a question whether it has any useful role. Here, the likelihood of telomere attrition in PD and its implications concerning microglia activation, ageing, oxidative stress, and the significance of telomerase activators are addressed. Also, the possibility of telomeres and telomerase as a diagnostic and therapeutic biomarker in PD is discussed. � 2023 Wiley-VCH GmbH.