Translational Omics in Neurodegenerative and Neurodevelopmental Disorders

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Molecular and Cellular Neuroscience".

Deadline for manuscript submissions: closed (8 January 2024) | Viewed by 4139

Special Issue Editors

Multi-Omics and Drug Discovery Lab, Chettinad Academy of Research and Education, Chennai 600130, India
Interests: multi-omics in neurodegenerative diseases; neuronal plasticity in Parkinson’s disease; neuronal systems biology; biomarkers and therapeutic target discovery; molecular modelling
Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Interests: cerebral ischemic stroke; neuroinflammation; neuroprotective drug discovery; diabetes and its complications especially microvascular; gene expression and epigenetic regulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The brain is one of the most precise and intricate organs, with functionally distinct regions, neuron circuits, and cell types. Neuronal development is complex and strictly regulated at both structural and functional levels. The neurodevelopment process is immensely reliant on the appropriate regulation of specific genes, epigenetics, protein expression, and lifestyle behaviors. Dysregulation of these during the neuronal development phase leads to a variety of diseases including, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), Tourette syndrome, Fragile X syndrome, and speech and language disorder. Alternatively, neurodegenerative diseases are more prominent in the elderly phase of life causing neuronal loss leading to Alzheimer's disease (AD), Parkinson's disease (PD), prion disease, and synucleionopathies. 

Recent high-throughput technologies have significantly extended the domains of genome, epigenome, transcriptome, proteome, and metabolome in neuropathogenesis. Certainly, these omics data can be integrated to define the relationship at various biological states from genome to metabolome, thereby accelerating research that aimed at identifying biomarkers, pharmaceutical targets, and personalized drugs and treatment by uncovering the mechanisms behind complex neurodevelopment disorders and neurodegenerative diseases.

The Special Issue of Brain Sciences aims to provide recent breakthrough research on multi-omics translational regulation in neurodegenerative and neurodevelopment disorders. We invite authors to submit their findings in the following version: research articles, short communication reports, and review articles on the translational application for the above-mentioned Special Issue.

Neurodevelopment disorders:

  • Identification of biomarkers to distinguish neurodevelopment disorders and diseases.
  • Diagnostics and therapeutic markers for neurodevelopment disorders.
  • Pathogenesis of neurodevelopment disorders.
  • Diagnostics and drug development.

Neurodegenerative diseases

  • Identification of biomarkers for neurodegenerative diseases.
  • Diagnostics and therapeutic markers for neurodegenerative diseases.
  • Neuroprotective role in neurodegenerative diseases.
  • Oxidative, inflammation, phagocytosis, and apoptosis markers to distinguish early or late tissue degeneration.
  • Diagnostics and drug development.

Dr. Shiek S.S.J. Ahmed
Dr. Prabu Paramasivam
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Neurodegeneration
  • Neurodevelopment
  • Omics
  • Translation regulation
  • Diagnostic biomarkers
  • Therapeutic targets

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

15 pages, 4026 KiB  
Article
Screening of Crucial Cytosolicproteins Interconnecting the Endoplasmic Reticulum and Mitochondria in Parkinson’s Disease and the Impact of Anti-Parkinson Drugs in the Preservation of Organelle Connectivity
by Athira Anirudhan, S. Mahema, Sheikh F. Ahmad, Talha Bin Emran, Shiek S. S. J. Ahmed and Prabu Paramasivam
Brain Sci. 2023, 13(11), 1551; https://doi.org/10.3390/brainsci13111551 - 05 Nov 2023
Viewed by 1100
Abstract
Mitochondrial dysfunction is well-established in Parkinson’s disease (PD); however, its dysfunctions associating with cell organelle connectivity remain unknown. We aimed to establish the crucial cytosolic protein involved in organelle connectivity between mitochondria and the endopalmic reticulum (ER) through a computational approach by constructing [...] Read more.
Mitochondrial dysfunction is well-established in Parkinson’s disease (PD); however, its dysfunctions associating with cell organelle connectivity remain unknown. We aimed to establish the crucial cytosolic protein involved in organelle connectivity between mitochondria and the endopalmic reticulum (ER) through a computational approach by constructing an organelle protein network to extract functional clusters presenting the crucial PD protein connecting organelles. Then, we assessed the influence of anti-parkinsonism drugs (n = 35) on the crucial protein through molecular docking and molecular dynamic simulation and further validated its gene expression in PD participants under, istradefylline (n = 25) and amantadine (n = 25) treatment. Based on our investigation, D-aspartate oxidase (DDO )protein was found to be the critical that connects both mitochondria and the ER. Further, molecular docking showed that istradefylline has a high affinity (−9.073 kcal/mol) against DDO protein, which may disrupt mitochondrial-ER connectivity. While amantadine (−4.53 kcal/mol) shows negligible effects against DDO that contribute to conformational changes in drug binding, Successively, DDO gene expression was downregulated in istradefylline-treated PD participants, which elucidated the likelihood of an istradefylline off-target mechanism. Overall, our findings illuminate the off-target effects of anti-parkinsonism medications on DDO protein, enabling the recommendation of off-target-free PD treatments. Full article
Show Figures

Graphical abstract

18 pages, 15572 KiB  
Article
Identification of Cuproptosis Clusters and Integrative Analyses in Parkinson’s Disease
by Moxuan Zhang, Wenjia Meng, Chong Liu, Huizhi Wang, Renpeng Li, Qiao Wang, Yuan Gao, Siyu Zhou, Tingting Du, Tianshuo Yuan, Lin Shi, Chunlei Han and Fangang Meng
Brain Sci. 2023, 13(7), 1015; https://doi.org/10.3390/brainsci13071015 - 30 Jun 2023
Cited by 1 | Viewed by 1157
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease; it mainly occurs in the elderly population. Cuproptosis is a newly discovered form of regulated cell death involved in the progression of various diseases. Combining multiple GEO datasets, we analyzed the expression profile [...] Read more.
Parkinson’s disease (PD) is the second most common neurodegenerative disease; it mainly occurs in the elderly population. Cuproptosis is a newly discovered form of regulated cell death involved in the progression of various diseases. Combining multiple GEO datasets, we analyzed the expression profile and immunity of cuproptosis-related genes (CRGs) in PD. Dysregulated CRGs and differential immune responses were identified between PD and non-PD substantia nigra. Two CRG clusters were defined in PD. Immune analysis suggested that CRG cluster 1 was characterized by a high immune response. The enrichment analysis showed that CRG cluster 1 was significantly enriched in immune activation pathways, such as the Notch pathway and the JAK-STAT pathway. KIAA0319, AGTR1, and SLC18A2 were selected as core genes based on the LASSO analysis. We built a nomogram that can predict the occurrence of PD based on the core genes. Further analysis found that the core genes were significantly correlated with tyrosine hydroxylase activity. This study systematically evaluated the relationship between cuproptosis and PD and established a predictive model for assessing the risk of cuproptosis subtypes and the outcome of PD patients. This study provides a new understanding of PD-related molecular mechanisms and provides new insights into the treatment of PD. Full article
Show Figures

Figure 1

16 pages, 1726 KiB  
Article
Eleven Crucial Pesticides Appear to Regulate Key Genes That Link MPTP Mechanism to Cause Parkinson’s Disease through the Selective Degeneration of Dopamine Neurons
by Athira Anirudhan, George Chandy Mattethra, Khalid J. Alzahrani, Hamsa Jameel Banjer, Fuad M. Alzahrani, Ibrahim F. Halawani, Shankargouda Patil, Ashutosh Sharma, Prabu Paramasivam and Shiek S. S. J. Ahmed
Brain Sci. 2023, 13(7), 1003; https://doi.org/10.3390/brainsci13071003 - 28 Jun 2023
Cited by 2 | Viewed by 1104
Abstract
Pesticides kill neurons, but the mechanism leading to selective dopaminergic loss in Parkinson’s disease (PD) is unknown. Understanding the pesticide’s effect on dopaminergic neurons (DA) can help to screen and treat PD. The critical uptake of pesticides by the membrane receptors at DA [...] Read more.
Pesticides kill neurons, but the mechanism leading to selective dopaminergic loss in Parkinson’s disease (PD) is unknown. Understanding the pesticide’s effect on dopaminergic neurons (DA) can help to screen and treat PD. The critical uptake of pesticides by the membrane receptors at DA is hypothesized to activate a signaling cascade and accelerate degeneration. Using MPTP as a reference, we demonstrate the mechanisms of eleven crucial pesticides through molecular docking, protein networks, regulatory pathways, and prioritization of key pesticide-regulating proteins. Participants were recruited and grouped into control and PD based on clinical characteristics as well as pesticide traces in their blood plasma. Then, qPCR was used to measure pesticide-associated gene expression in peripheral blood mononuclear cells between groups. As a result of molecular docking, all eleven pesticides and the MPTP showed high binding efficiency against 274 membrane receptor proteins of DA. Further, the protein interaction networks showed activation of multiple signaling cascades through these receptors. Subsequent analysis revealed 31 biological pathways shared by all 11pesticides and MPTP that were overrepresented by 46 crucial proteins. Among these, CTNNB1, NDUFS6, and CAV1 were prioritized to show a significant change in gene expression in pesticide-exposed PD which guides toward therapy. Full article
Show Figures

Figure 1

Back to TopTop