Topic Editors

Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
Dr. Chuanbin Yang
1. Department of Geriatrics, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China
2. The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China
The Pritzker School of Molecular Engineering, Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA

Advances in Diagnostics, Brain Delivery Systems and Therapeutics of Neurodegenerative Disease

Abstract submission deadline
11 March 2025
Manuscript submission deadline
11 June 2025
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9898

Topic Information

Dear Colleagues,

Alzheimer’s disease (AD) is an age-associated neurodegenerative disease (ND) affecting social and behavioral activities. Prevalent studies indicate that the global AD population will reach 114 million by 2050. Presently, AD remains incurable, and the high failure rate of clinical trials for AD-related drugs has raised the need to understand the molecular mechanisms of AD. In addition, there is an utmost need to develop novel drugs as therapeutics and theranostic approaches for the early detection of AD progression and to target the molecular-level brain delivery of small molecules using nanocapsules as therapeutics for AD. Using advanced technology for the treatment of AD in diagnostics, brain delivery, and therapeutics will result in a bench-to-bedside solution in AD therapy. The application of advanced technology in drug discovery, diagnostics, and brain delivery systems has been flourishing in recent years for the remedy of Alzheimer’s disease. Inter-disciplinary approaches and strategies have helped understand the prognosis and pathogenesis of Alzheimer’s disease (AD). Unfortunately, there are no single confirmatory tests or diagnostics that can clinically be used to identify and determine the presence or absence of Alzheimer’s pathology. Therefore, AD has posed tremendous challenges for researchers in the scientific community and medical experts to tackle the unresolved issues in early detection, diagnostics, and therapeutics for AD.

Dr. Ashok Iyaswamy
Dr. Chuanbin Yang
Dr. Abhimanyu Thakur
Topic Editors

Keywords

  • Alzheimer’s disease
  • diagnostic probes
  • exosomes
  • small molecules
  • therapeutic agents
  • autophagy inducers
  • aptamers

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Biomolecules
biomolecules
5.5 8.3 2011 16.9 Days CHF 2700 Submit
International Journal of Molecular Sciences
ijms
5.6 7.8 2000 16.3 Days CHF 2900 Submit
Molecules
molecules
4.6 6.7 1996 14.6 Days CHF 2700 Submit
Pharmaceutics
pharmaceutics
5.4 6.9 2009 14.2 Days CHF 2900 Submit

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Published Papers (8 papers)

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15 pages, 693 KiB  
Review
Switching On/Off Amyloid Plaque Formation in Transgenic Animal Models of Alzheimer’s Disease
by Sergey A. Kozin, Olga I. Kechko, Alexei A. Adzhubei, Alexander A. Makarov and Vladimir A. Mitkevich
Int. J. Mol. Sci. 2024, 25(1), 72; https://doi.org/10.3390/ijms25010072 - 20 Dec 2023
Viewed by 1192
Abstract
A hallmark of Alzheimer’s disease (AD) are the proteinaceous aggregates formed by the amyloid-beta peptide (Aβ) that is deposited inside the brain as amyloid plaques. The accumulation of aggregated Aβ may initiate or enhance pathologic processes in AD. According to the amyloid hypothesis, [...] Read more.
A hallmark of Alzheimer’s disease (AD) are the proteinaceous aggregates formed by the amyloid-beta peptide (Aβ) that is deposited inside the brain as amyloid plaques. The accumulation of aggregated Aβ may initiate or enhance pathologic processes in AD. According to the amyloid hypothesis, any agent that has the capability to inhibit Aβ aggregation and/or destroy amyloid plaques represents a potential disease-modifying drug. In 2023, a humanized IgG1 monoclonal antibody (lecanemab) against the Aβ-soluble protofibrils was approved by the US FDA for AD therapy, thus providing compelling support to the amyloid hypothesis. To acquire a deeper insight on the in vivo Aβ aggregation, various animal models, including aged herbivores and carnivores, non-human primates, transgenic rodents, fish and worms were widely exploited. This review is based on the recent data obtained using transgenic animal AD models and presents experimental verification of the critical role in Aβ aggregation seeding of the interactions between zinc ions, Aβ with the isomerized Asp7 (isoD7-Aβ) and the α4β2 nicotinic acetylcholine receptor. Full article
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20 pages, 5029 KiB  
Article
Integrative Analysis of Machine Learning and Molecule Docking Simulations for Ischemic Stroke Diagnosis and Therapy
by Jingwei Song, Syed Aqib Ali Zaidi, Liangge He, Shuai Zhang and Guangqian Zhou
Molecules 2023, 28(23), 7704; https://doi.org/10.3390/molecules28237704 - 22 Nov 2023
Viewed by 1021
Abstract
Due to the narrow therapeutic window and high mortality of ischemic stroke, it is of great significance to investigate its diagnosis and therapy. We employed weighted gene coexpression network analysis (WGCNA) to ascertain gene modules related to stroke and used the maSigPro R [...] Read more.
Due to the narrow therapeutic window and high mortality of ischemic stroke, it is of great significance to investigate its diagnosis and therapy. We employed weighted gene coexpression network analysis (WGCNA) to ascertain gene modules related to stroke and used the maSigPro R package to seek the time-dependent genes in the progression of stroke. Three machine learning algorithms were further employed to identify the feature genes of stroke. A nomogram model was built and applied to evaluate the stroke patients. We analyzed single-cell RNA sequencing (scRNA-seq) data to discern microglia subclusters in ischemic stroke. The RNA velocity, pseudo time, and gene set enrichment analysis (GSEA) were performed to investigate the relationship of microglia subclusters. Connectivity map (CMap) analysis and molecule docking were used to screen a therapeutic agent for stroke. A nomogram model based on the feature genes showed a clinical net benefit and enabled an accurate evaluation of stroke patients. The RNA velocity and pseudo time analysis showed that microglia subcluster 0 would develop toward subcluster 2 within 24 h from stroke onset. The GSEA showed that the function of microglia subcluster 0 was opposite to that of subcluster 2. AZ_628, which screened from CMap analysis, was found to have lower binding energy with Mmp12, Lgals3, Fam20c, Capg, Pkm2, Sdc4, and Itga5 in microglia subcluster 2 and maybe a therapeutic agent for the poor development of microglia subcluster 2 after stroke. Our study presents a nomogram model for stroke diagnosis and provides a potential molecule agent for stroke therapy. Full article
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18 pages, 2635 KiB  
Article
Searching for Metabolic Markers of Stroke in Human Plasma via NMR Analysis
by Nádia Oliveira, Adriana Sousa, Ana Paula Amaral, Gonçalo Graça and Ignacio Verde
Int. J. Mol. Sci. 2023, 24(22), 16173; https://doi.org/10.3390/ijms242216173 - 10 Nov 2023
Viewed by 892
Abstract
More than 12 million people around the world suffer a stroke every year, one every 3 s. Stroke has a variety of causes and is often the result of a complex interaction of risk factors related to age, genetics, gender, lifestyle, and some [...] Read more.
More than 12 million people around the world suffer a stroke every year, one every 3 s. Stroke has a variety of causes and is often the result of a complex interaction of risk factors related to age, genetics, gender, lifestyle, and some cardiovascular and metabolic diseases. Despite this evidence, it is not possible to prevent the onset of stroke. The use of innovative methods for metabolite analysis has been explored in the last years to detect new stroke biomarkers. We use NMR spectroscopy to identify small molecule variations between different stages of stroke risk. The Framingham Stroke Risk Score was used in people over 63 years of age living in long-term care facilities (LTCF) to calculate the probability of suffering a stroke. Using this parameter, three study groups were formed: low stroke risk (LSR, control), moderate stroke risk (MSR) and high stroke risk (HSR). Univariate statistical analysis showed seven metabolites with increasing plasma levels across different stroke risk groups, from LSR to HSR: isoleucine, asparagine, formate, creatinine, dimethylsulfone and two unidentified molecules, which we termed “unknown-1” and “unknown-3”. These metabolic markers can be used for early detection and to detect increasing stages of stroke risk more efficiently. Full article
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17 pages, 5642 KiB  
Article
PHB2 Alleviates Neurotoxicity of Prion Peptide PrP106–126 via PINK1/Parkin-Dependent Mitophagy
by Xiaohui Zheng, Kun Liu, Qingqing Xie, Hangkuo Xin, Wei Chen, Shengyu Lin, Danqi Feng and Ting Zhu
Int. J. Mol. Sci. 2023, 24(21), 15919; https://doi.org/10.3390/ijms242115919 - 02 Nov 2023
Viewed by 870
Abstract
Prion diseases are a group of neurodegenerative diseases characterized by mitochondrial dysfunction and neuronal death. Mitophagy is a selective form of macroautophagy that clears injured mitochondria. Prohibitin 2 (PHB2) has been identified as a novel inner membrane mitophagy receptor that mediates mitophagy. However, [...] Read more.
Prion diseases are a group of neurodegenerative diseases characterized by mitochondrial dysfunction and neuronal death. Mitophagy is a selective form of macroautophagy that clears injured mitochondria. Prohibitin 2 (PHB2) has been identified as a novel inner membrane mitophagy receptor that mediates mitophagy. However, the role of PHB2 in prion diseases remains unclear. In this study, we isolated primary cortical neurons from rats and used the neurotoxic prion peptide PrP106–126 as a cell model for prion diseases. We examined the role of PHB2 in PrP106–126-induced mitophagy using Western blotting and immunofluorescence microscopy and assessed the function of PHB2 in PrP106–126-induced neuronal death using the cell viability assay and the TUNEL assay. The results showed that PrP106–126 induced mitochondrial morphological abnormalities and mitophagy in primary cortical neurons. PHB2 was found to be indispensable for PrP106–126-induced mitophagy and was involved in the accumulation of PINK1 and recruitment of Parkin to mitochondria in primary neurons. Additionally, PHB2 depletion exacerbated neuronal cell death induced by PrP106–126, whereas the overexpression of PHB2 alleviated PrP106–126 neuronal toxicity. Taken together, this study demonstrated that PHB2 is indispensable for PINK1/Parkin-mediated mitophagy in PrP106–126-treated neurons and protects neurons against the neurotoxicity of the prion peptide. Full article
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13 pages, 2629 KiB  
Article
Analysis of Potential Biomarkers in Frontal Temporal Dementia: A Bioinformatics Approach
by Inara Deedar Momin, Jessica Rigler and Kumaraswamy Naidu Chitrala
Int. J. Mol. Sci. 2023, 24(19), 14910; https://doi.org/10.3390/ijms241914910 - 05 Oct 2023
Viewed by 1201
Abstract
Frontal temporal dementia (FTD) is a neurological disorder known to have fewer therapeutic options. So far, only a few biomarkers are available for FTD that can be used as potential comorbidity targets. For example, genes such as VCP, which has a role [...] Read more.
Frontal temporal dementia (FTD) is a neurological disorder known to have fewer therapeutic options. So far, only a few biomarkers are available for FTD that can be used as potential comorbidity targets. For example, genes such as VCP, which has a role in breast cancer, and WFS1, which has a role in COVID-19, are known to show a role in FTD as well. To this end, in the present study, we aim to identify potential biomarkers or susceptible genes for FTD that show comorbidities with diseases such as COVID-19 and breast cancer. A dataset from Gene Expression Omnibus containing FTD expression profiles from African American and white ethnicity backgrounds was included in our study. In FTD samples of the GSE193391 dataset, we identified 305 DEGs, with 168 genes being up-regulated and 137 genes being down-regulated. We conducted a comorbidity analysis for COVID-19 and breast cancer, followed by an analysis of potential drug interactions, pathogenicity, analysis of genetic variants, and functional enrichment analysis. Our results showed that the genes AKT3, GFAP, ADCYAP1R1, VDAC1, and C4A have significant transcriptomic alterations in FTD along with the comorbidity status with COVID-19 and breast cancer. Functional pathway analysis revealed that these comorbid genes were significantly enriched in the pathways such as glioma, JAK/STAT signaling, systematic lupus erythematosus, neurodegeneration-multiple diseases, and neuroactive ligand–receptor interaction. Overall, from these results, we concluded that these genes could be recommended as potential therapeutic targets for the treatment of comorbidities (breast cancer and COVID-19) in patients with FTD. Full article
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40 pages, 1743 KiB  
Article
Chirality Matters: Fine-Tuning of Novel Monoamine Reuptake Inhibitors Selectivity through Manipulation of Stereochemistry
by Predrag Kalaba, Katharina Pacher, Philip John Neill, Vladimir Dragacevic, Martin Zehl, Judith Wackerlig, Michael Kirchhofer, Simone B. Sartori, Hubert Gstach, Shima Kouhnavardi, Anna Fabisikova, Matthias Pillwein, Francisco Monje-Quiroga, Karl Ebner, Alexander Prado-Roller, Nicolas Singewald, Ernst Urban, Thierry Langer, Christian Pifl, Jana Lubec, Johann Jakob Leban and Gert Lubecadd Show full author list remove Hide full author list
Biomolecules 2023, 13(9), 1415; https://doi.org/10.3390/biom13091415 - 19 Sep 2023
Cited by 1 | Viewed by 1045
Abstract
The high structural similarity, especially in transmembrane regions, of dopamine, norepinephrine, and serotonin transporters, as well as the lack of all crystal structures of human isoforms, make the specific targeting of individual transporters rather challenging. Ligand design itself is also rather limited, as [...] Read more.
The high structural similarity, especially in transmembrane regions, of dopamine, norepinephrine, and serotonin transporters, as well as the lack of all crystal structures of human isoforms, make the specific targeting of individual transporters rather challenging. Ligand design itself is also rather limited, as many chemists, fully aware of the synthetic and analytical challenges, tend to modify lead compounds in a way that reduces the number of chiral centers and hence limits the potential chemical space of synthetic ligands. We have previously shown that increasing molecular complexity by introducing additional chiral centers ultimately leads to more selective and potent dopamine reuptake inhibitors. Herein, we significantly extend our structure-activity relationship of dopamine transporter-selective ligands and further demonstrate how stereoisomers of defined absolute configuration may fine-tune and direct the activity towards distinct targets. From the pool of active compounds, using the examples of stereoisomers 7h and 8h, we further showcase how in vitro activity significantly differs in in vivo drug efficacy experiments, calling for proper validation of individual stereoisomers in animal studies. Furthermore, by generating a large library of compounds with defined absolute configurations, we lay the groundwork for computational chemists to further optimize and rationally design specific monoamine transporter reuptake inhibitors. Full article
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15 pages, 991 KiB  
Review
Blood-Based Biomarkers in the Diagnosis of Chronic Traumatic Encephalopathy: Research to Date and Future Directions
by Michal J. Halicki, Karen Hind and Paul L. Chazot
Int. J. Mol. Sci. 2023, 24(16), 12556; https://doi.org/10.3390/ijms241612556 - 08 Aug 2023
Viewed by 1808
Abstract
Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease consistently associated with repetitive traumatic brain injuries (TBIs), which makes multiple professions, such as contact sports athletes and the military, especially susceptible to its onset. There are currently no approved biomarkers to diagnose CTE, thus [...] Read more.
Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease consistently associated with repetitive traumatic brain injuries (TBIs), which makes multiple professions, such as contact sports athletes and the military, especially susceptible to its onset. There are currently no approved biomarkers to diagnose CTE, thus it can only be confirmed through a post-mortem brain autopsy. Several imaging and cerebrospinal fluid biomarkers have shown promise in the diagnosis. However, blood-based biomarkers can be more easily obtained and quantified, increasing their clinical feasibility and potential for prophylactic use. This article aimed to comprehensively review the studies into potential blood-based biomarkers of CTE, discussing common themes and limitations, as well as suggesting future research directions. While the interest in blood-based biomarkers of CTE has recently increased, the research is still in its early stages. The main issue for many proposed biomarkers is their lack of selectivity for CTE. However, several molecules, such as different phosphorylated tau isoforms, were able to discern CTE from different neurodegenerative diseases. Further, the results from studies on exosomal biomarkers suggest that exosomes are a promising source of biomarkers, reflective of the internal environment of the brain. Nonetheless, more longitudinal studies combining imaging, neurobehavioral, and biochemical approaches are warranted to establish robust biomarkers for CTE. Full article
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18 pages, 1726 KiB  
Review
MicroRNAs-Based Theranostics against Anesthetic-Induced Neurotoxicity
by Roseleena Minz, Praveen Kumar Sharma, Arvind Negi and Kavindra Kumar Kesari
Pharmaceutics 2023, 15(7), 1833; https://doi.org/10.3390/pharmaceutics15071833 - 27 Jun 2023
Cited by 1 | Viewed by 1137
Abstract
Various clinical reports indicate prolonged exposure to general anesthetic-induced neurotoxicity (in vitro and in vivo). Behavior changes (memory and cognition) are compilations commonly cited with general anesthetics. The ability of miRNAs to modulate gene expression, thereby selectively altering cellular functions, remains one of [...] Read more.
Various clinical reports indicate prolonged exposure to general anesthetic-induced neurotoxicity (in vitro and in vivo). Behavior changes (memory and cognition) are compilations commonly cited with general anesthetics. The ability of miRNAs to modulate gene expression, thereby selectively altering cellular functions, remains one of the emerging techniques in the recent decade. Importantly, engineered miRNAs (which are of the two categories, i.e., agomir and antagomir) to an extent found to mitigate neurotoxicity. Utilizing pre-designed synthetic miRNA oligos would be an ideal analeptic approach for intervention based on indicative parameters. This review demonstrates engineered miRNA’s potential as prophylactics and/or therapeutics minimizing the general anesthetics-induced neurotoxicity. Furthermore, we share our thoughts regarding the current challenges and feasibility of using miRNAs as therapeutic agents to counteract the adverse neurological effects. Moreover, we discuss the scientific status and updates on the novel neuro-miRNAs related to therapy against neurotoxicity induced by amyloid beta (Aβ) and Parkinson’s disease (PD). Full article
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