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Article ; Online: Correction: Association of Biochemical Parameters and Screening for Mutations in the MCU Gene in Alzheimer's Disease Patients.

Venugopal, Anila / Iyer, Mahalaxmi / Narayanasamy, Arul / Ravimanickam, T / Gopalakrishnan, Abilash Valsala / Yadav, Mukesh Kumar / Kumar, Nachimuthu Senthil / Vellingiri, Balachandar

Molecular neurobiology

2024

Language	English
Publishing date	2024-01-22
Publishing country	United States
Document type	Published Erratum
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-024-03929-8
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Article ; Online: Midbrain organoids for Parkinson's disease (PD) - A powerful tool to understand the disease pathogenesis.

Babu, Harysh Winster Suresh / Kumar, Sindduja Muthu / Kaur, Harsimrat / Iyer, Mahalaxmi / Vellingiri, Balachandar

Life sciences

2024 Volume 345, Page(s) 122610

Abstract: Brain Organiods (BOs) are a promising technique for researching disease progression in the human brain. These organoids, which are produced from human induced pluripotent stem cells (HiPSCs), can construct themselves into structured frameworks. In the ... ...

Abstract	Brain Organiods (BOs) are a promising technique for researching disease progression in the human brain. These organoids, which are produced from human induced pluripotent stem cells (HiPSCs), can construct themselves into structured frameworks. In the context of Parkinson's disease (PD), recent advancements have been made in the development of Midbrain organoids (MBOs) models that consider key pathophysiological mechanisms such as alpha-synuclein (α-Syn), Lewy bodies, dopamine loss, and microglia activation. However, there are limitations to the current use of BOs in disease modelling and drug discovery, such as the lack of vascularization, long-term differentiation, and absence of glial cells. To address these limitations, researchers have proposed the use of spinning bioreactors to improve oxygen and nutrient perfusion. Modelling PD utilising modern experimental in vitro models is a valuable tool for studying disease mechanisms and elucidating previously unknown features of PD. In this paper, we exclusively review the unique methods available for cultivating MBOs using a pumping system that mimics the circulatory system. This mechanism may aid in delivering the required amount of oxygen and nutrients to all areas of the organoids, preventing cell death, and allowing for long-term culture and using co-culturing techniques for developing glial cell in BOs. Furthermore, we emphasise some of the significant discoveries about the BOs and the potential challenges of using BOs will be discussed.
MeSH term(s)	Humans ; Parkinson Disease/metabolism ; Induced Pluripotent Stem Cells ; alpha-Synuclein/metabolism ; Mesencephalon/metabolism ; Mesencephalon/pathology ; Organoids/metabolism ; Oxygen/metabolism ; Dopaminergic Neurons/metabolism
Chemical Substances	alpha-Synuclein ; Oxygen (S88TT14065)
Language	English
Publishing date	2024-04-03
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2024.122610
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Article ; Online: Highlighting novel genes associated with the classical Rett syndrome patient from India.

Mohan, Gomathi / Sarma, Ranjan Jyoti / Iyer, Mahalaxmi / Kumar, Nachimuthu Senthil / Vellingiri, Balachandar

Genes & diseases

2022 Volume 9, Issue 6, Page(s) 1394–1396

Language	English
Publishing date	2022-01-06
Publishing country	China
Document type	Journal Article
ZDB-ID	2821806-1
ISSN	2352-3042 ; 2352-3042
ISSN (online)	2352-3042
ISSN	2352-3042
DOI	10.1016/j.gendis.2021.12.002
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Article ; Online: Corrigendum to "a review of chromium (Cr) epigenetic toxicity and health hazards" [Sci. Total environ., volume 882, 1-12, 15 July 2023, 163,483].

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 / Barceló, Damià / Vellingiri, Balachandar

The Science of the total environment

2024 Volume 914, Page(s) 169798

Language	English
Publishing date	2024-01-15
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2023.169798
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Article ; Online: Artificial intelligence and machine learning algorithms in the detection of heavy metals in water and wastewater: Methodological and ethical challenges.

Maurya, Brij Mohan / Yadav, Nidhi / T, Amudha / J, Satheeshkumar / A, Sangeetha / V, Parthasarathy / Iyer, Mahalaxmi / Yadav, Mukesh Kumar / Vellingiri, Balachandar

Chemosphere

2024 Volume 353, Page(s) 141474

Abstract: Heavy metals (HMs) enter waterbodies through various means, which, when exceeding a threshold limit, cause toxic effects both on the environment and in humans upon entering their systems. Recent times have seen an increase in such HM influx incident ... ...

Abstract	Heavy metals (HMs) enter waterbodies through various means, which, when exceeding a threshold limit, cause toxic effects both on the environment and in humans upon entering their systems. Recent times have seen an increase in such HM influx incident rates. This requires an instant response in this regard to review the challenges in the available classical methods for HM detection and removal. As well as provide an opportunity to explore the applications of artificial intelligence (AI) and machine learning (ML) for the identification and further redemption of water and wastewater from the HMs. This review of research focuses on such applications in conjunction with the available in-silico models producing worldwide data for HM levels. Furthermore, the effect of HMs on various disease progressions has been provided, along with a brief account of prediction models analysing the health impact of HM intoxication. Also discussing the ethical and other challenges associated with the use of AI and ML in this field is the futuristic approach intended to follow, opening a wide scope of possibilities for improvement in wastewater treatment methodologies.
MeSH term(s)	Humans ; Artificial Intelligence ; Wastewater ; Water/analysis ; Algorithms ; Machine Learning ; Metals, Heavy/analysis
Chemical Substances	Wastewater ; Water (059QF0KO0R) ; Metals, Heavy
Language	English
Publishing date	2024-02-19
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	120089-6
ISSN	1879-1298 ; 0045-6535 ; 0366-7111
ISSN (online)	1879-1298
ISSN	0045-6535 ; 0366-7111
DOI	10.1016/j.chemosphere.2024.141474
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Article ; Online: Leber's hereditary optic neuropathy: Current approaches and future perspectives on Mesenchymal stem cell-mediated rescue.

Mohana Devi, Subramaniam / Abishek Kumar, B / Mahalaxmi, Iyer / Balachandar, Vellingiri

Mitochondrion

2021 Volume 60, Page(s) 201–218

Abstract: Leber's Hereditary Optic Neuropathy (LHON) is an inherited optic nerve disorder. It is a mitochondrially inherited disease due to point mutation in the MT-ND1, MT-ND4, and MT-ND6 genes of mitochondrial DNA (mtDNA) coding for complex I subunit proteins. ... ...

Abstract	Leber's Hereditary Optic Neuropathy (LHON) is an inherited optic nerve disorder. It is a mitochondrially inherited disease due to point mutation in the MT-ND1, MT-ND4, and MT-ND6 genes of mitochondrial DNA (mtDNA) coding for complex I subunit proteins. These mutations affect the assembly of the mitochondrial complex I and hence the electron transport chain leading to mitochondrial dysfunction and oxidative damage. Optic nerve cells like retinal ganglion cells (RGCs) are more sensitive to mitochondrial loss and oxidative damage which results in the progressive degeneration of RGCs at the axonal region of the optic nerve leading to bilateral vision loss. Currently, gene therapy using Adeno-associated viral vector (AAV) is widely studied for the therapeutics application in LHON. Our review highlights the application of cell-based therapy for LHON. Mesenchymal stem cells (MSCs) are known to rescue cells from the pre-apoptotic stage by transferring healthy mitochondria through tunneling nanotubes (TNT) for cellular oxidative function. Empowering the transfer of healthy mitochondria using MSCs may replace the mitochondria with pathogenic mutation and possibly benefit the cells from progressive damage. This review discusses the ongoing research in LHON and mitochondrial transfer mechanisms to explore its scope in inherited optic neuropathy.
MeSH term(s)	Humans ; Mesenchymal Stem Cell Transplantation ; Optic Atrophy, Hereditary, Leber/therapy
Language	English
Publishing date	2021-08-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2056923-3
ISSN	1872-8278 ; 1567-7249
ISSN (online)	1872-8278
ISSN	1567-7249
DOI	10.1016/j.mito.2021.08.013
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Article ; Online: Dysfunction in Mitochondrial Electron Transport Chain Complex I, Pyruvate Dehydrogenase Activity, and Mutations in ND1 and ND4 Gene in Autism Spectrum Disorder Subjects from Tamil Nadu Population, India.

Mahalaxmi, Iyer / Subramaniam, Mohana Devi / Gopalakrishnan, Abilash Valsala / Vellingiri, Balachandar

Molecular neurobiology

2021 Volume 58, Issue 10, Page(s) 5303–5311

Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by impaired social interaction and behavioural abnormalities. Growing evidence proved that impairment in mitochondrial functions could inhibit energy production and may ... ...

Abstract	Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by impaired social interaction and behavioural abnormalities. Growing evidence proved that impairment in mitochondrial functions could inhibit energy production and may contribute to the onset of ASD. Genetic variants in the genes of mitochondrial DNA (mtDNA) could interrupt the normal energy metabolism and production in the brain which lead to a wide range of structural and functional changes in the brain resulting in ASD. The present study aims to compare the activities of mitochondrial electron transport chain (ETC) complex I, pyruvate dehydrogenase (PDH) and specific mitochondrial DNA gene (MT-ND1 and MT-ND4) variants associated with ASD subjects in the Tamil Nadu population. Mutational analysis revealed that most mutations in ASD subjects showed synonymous type followed by missense in both the ND1 and ND4 genes. Interestingly, we found that the complex I and PDH dysfunctions may have a role in ASD compared to the controls (p ≤ 0.0001). Hence, the results of the present study suggest that mitochondrial dysfunction, specifically the complex I genes, may play a major role in the onset of ASD, concluding that further research on mitochondrial genes are mandatory to unravel the mechanism behind ASD pathogenesis.
MeSH term(s)	Adolescent ; Autism Spectrum Disorder/epidemiology ; Autism Spectrum Disorder/genetics ; Autism Spectrum Disorder/metabolism ; Child ; Child, Preschool ; DNA, Mitochondrial/genetics ; DNA, Mitochondrial/metabolism ; Electron Transport Complex I/genetics ; Electron Transport Complex I/metabolism ; Enzyme Activation/physiology ; Female ; Humans ; India/epidemiology ; Male ; Mutation/genetics ; NADH Dehydrogenase/genetics ; Polymorphism, Single Nucleotide/genetics ; Population Surveillance ; Pyruvate Dehydrogenase Complex/genetics ; Pyruvate Dehydrogenase Complex/metabolism
Chemical Substances	DNA, Mitochondrial ; NADH dehydrogenase subunit 4 ; Pyruvate Dehydrogenase Complex ; NADH Dehydrogenase (EC 1.6.99.3) ; NADH dehydrogenase subunit 1, human (EC 1.6.99.3) ; Electron Transport Complex I (EC 7.1.1.2)
Language	English
Publishing date	2021-07-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-021-02492-w
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Article ; Online: Plausible Role of Mitochondrial DNA Copy Number in Neurodegeneration-a Need for Therapeutic Approach in Parkinson's Disease (PD).

Venkatesan, Dhivya / Iyer, Mahalaxmi / Narayanasamy, Arul / Gopalakrishnan, Abilash Valsala / Vellingiri, Balachandar

Molecular neurobiology

2023 Volume 60, Issue 12, Page(s) 6992–7008

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; DNA, Mitochondrial/genetics ; DNA, Mitochondrial/metabolism ; Parkinson Disease/genetics ; Parkinson Disease/therapy ; Parkinson Disease/metabolism ; DNA Copy Number Variations/genetics ; Mitochondria/metabolism ; Neurons/metabolism
Chemical Substances	DNA, Mitochondrial
Language	English
Publishing date	2023-07-31
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-023-03500-x
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Article ; Online: Advantages of mesenchymal stem cell over the other stem cells.

Gopalarethinam, Janani / Nair, Aswathy P / Iyer, Mahalaxmi / Vellingiri, Balachandar / Subramaniam, Mohana Devi

Acta histochemica

2023 Volume 125, Issue 4, Page(s) 152041

Abstract: A stem cell is a particular group of cells that has the extraordinary potential to convert within the body into particular cell types. They are used to regenerate tissues and cells in the body that have been damaged or destroyed by the disease. Stem ... ...

Abstract	A stem cell is a particular group of cells that has the extraordinary potential to convert within the body into particular cell types. They are used to regenerate tissues and cells in the body that have been damaged or destroyed by the disease. Stem cells come in three different varieties: adult stem cells, embryonic stem cells and induced pluripotent stem cells (iPSCs). Embryonic stem cells have a high chance of immune rejection and also have ethical dilemmas and iPSCs have genetic instability. Adult stem cells are difficult to analyze and extract for research since they are frequently insufficient in native tissues. However, mesenchymal stem cells (MSC) one of the categories of adult stem cells are stromal cells with a variety of potentials that can differentiate into a wide range of cell types. MSCs can be transplanted into a variety of people without worrying about rejection because they have demonstrated the ability to prevent an adverse reaction from the immune system. These transplants have powerful anti-inflammatory and immunosuppressive effects and greatly enhance the body's inherent healing capacity. While MSCs do not offer treatment for illnesses, the idea behind them is to enable the body to recover sufficiently for a protracted reduction in symptoms. In many cases, this is sufficient to significantly enhance the patient's well-being. Inspite of several advantages some potential long-term concerns connected to MSC therapy are maldifferentiation, immunosuppression and cancerous tumor growth. In this review, we will compare the mesenchymal stem cells with other stem cells with respect to the source of origin, their properties and therapeutic applications, and discuss the MSC's disadvantages.
MeSH term(s)	Adult ; Humans ; Mesenchymal Stem Cells ; Embryonic Stem Cells ; Induced Pluripotent Stem Cells/metabolism ; Signal Transduction ; Mesenchymal Stem Cell Transplantation/methods
Language	English
Publishing date	2023-05-09
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	77-2
ISSN	1618-0372 ; 0065-1281
ISSN (online)	1618-0372
ISSN	0065-1281
DOI	10.1016/j.acthis.2023.152041
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Article ; Online: Untangle the mystery behind DS-associated AD - Is APP the main protagonist?

Elangovan, Ajay / Babu, Harysh Winster Suresh / Iyer, Mahalaxmi / Gopalakrishnan, Abilash Valsala / Vellingiri, Balachandar

Ageing research reviews

2023 Volume 87, Page(s) 101930

Abstract: Amyloid precursor protein profusion in Trisomy 21, also called Down Syndrome (DS), is rooted in the genetic determination of Alzheimer's disease (AD). With the recent development in patient care, the life expectancy of DS patients has gradually increased, ...

Abstract	Amyloid precursor protein profusion in Trisomy 21, also called Down Syndrome (DS), is rooted in the genetic determination of Alzheimer's disease (AD). With the recent development in patient care, the life expectancy of DS patients has gradually increased, leading to the high prospect of AD development, consequently leading to the development of plaques of amyloid proteins and neurofibrillary tangles made of tau by the fourth decade of the patient leading to dementia. The altered gene expression resulted in cellular dysfunction due to impairment of autophagy, mitochondrial and lysosomal dysfunction, and copy number variation controlled by the additional genes in Trisomy 21. The cognitive impairment and mechanistic insights underlying DS-AD conditions have been reviewed in this article. Some recent findings regarding biomarkers and therapeutics of DS-AD conditions were highlighted in this review.
MeSH term(s)	Humans ; Alzheimer Disease/metabolism ; Down Syndrome/genetics ; Down Syndrome/metabolism ; DNA Copy Number Variations ; Amyloid beta-Protein Precursor/genetics ; Amyloid beta-Protein Precursor/metabolism ; Neurofibrillary Tangles/metabolism ; Amyloid beta-Peptides/metabolism ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Protein Precursor ; Amyloid beta-Peptides ; tau Proteins
Language	English
Publishing date	2023-04-07
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2075672-0
ISSN	1872-9649 ; 1568-1637
ISSN (online)	1872-9649
ISSN	1568-1637
DOI	10.1016/j.arr.2023.101930
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