Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
Challenges and Innovation in Neurodegenerative Diseases
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Challenges and Innovation in Neurodegenerative Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (30 May 2024) | Viewed by 17566

Special Issue Editor

Dr. King-Ho Cheung

E-Mail Website
Guest Editor
School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China
Interests: ion channels; electrophysiology; epithelial transport; Alzheimer’s disease; neurodegenerative diseases; new drug development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The umbrella of neurodegeneration covers a group of heterogeneous diseases including Alzheimer's disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and others that account for more than 5% of the global burden of all diseases. Although considerable advances in understanding the triggers of neurodegenerative diseases had led to the development of new drugs, there are a handful of challenges that remain in the field that we must overcome to allow cures for the diseases. For example, good disease models that more faithfully recapitulate human disease are devastatingly needed. A full understanding of the involvement of protein aggregation in disease progression and the identification of disease-specific biomarkers would allow the early detection of neurodegeneration and permit reliable disease progression monitoring. The recent application of machine learning and artificial intelligence in new drug discovery and development from natural products as well as the use of stem cell therapy also brings hope to patients with neurodegenerative diseases.

This Special Issue aims to collect views on the current challenges in the field, the exciting progress in deciphering the disease pathogenesis, and the cutting-edge technologies for the early detection of neurodegeneration. The accumulation of innovative findings in these areas may pave the way for the development of therapeutic interventions for neurogenerative diseases.

Dr. King-Ho Cheung
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • neurodegenerative diseases
  • pathogenesis
  • biomarkers
  • disease model
  • natural product
  • new drug discovery
  • therapy
  • machine learning
  • stem cell therapy

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Related Special Issue

Published Papers (9 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

13 pages, 261 KiB  
Article
Cytokine Profiling in Cerebrospinal Fluid of Patients with Newly Diagnosed Relapsing-Remitting Multiple Sclerosis (RRMS): Associations between Inflammatory Biomarkers and Disease Activity
by Barbara Gębka-Kępińska, Bożena Adamczyk, Dorota Gębka, Zenon Czuba, Jarosław Szczygieł and Monika Adamczyk-Sowa
Int. J. Mol. Sci. 2024, 25(13), 7399; https://doi.org/10.3390/ijms25137399 - 5 Jul 2024
Cited by 1 | Viewed by 1072
Abstract
Cytokines regulate immune responses and are crucial to MS pathogenesis. This study evaluated pro-inflammatory and anti-inflammatory cytokine concentrations in the CSF of de novo diagnosed RRMS patients compared to healthy controls. We assessed cytokine levels in the CSF of 118 de novo diagnosed [...] Read more.
Cytokines regulate immune responses and are crucial to MS pathogenesis. This study evaluated pro-inflammatory and anti-inflammatory cytokine concentrations in the CSF of de novo diagnosed RRMS patients compared to healthy controls. We assessed cytokine levels in the CSF of 118 de novo diagnosed RRMS patients and 112 controls, analyzing relationships with time from symptom onset to diagnosis, MRI lesions, and serum vitamin D levels. Elevated levels of IL-2, IL-4, IL-6, IL-13, FGF-basic, and GM-CSF, and lower levels of IL-1β, IL-1RA, IL-5, IL-7, IL-9, IL-10, IL-12p70, IL-15, G-CSF, PDGF-bb, and VEGF were observed in RRMS patients compared to controls. IL-2, IL-4, IL-12p70, PDGF, G-CSF, GM-CSF, and FGF-basic levels increased over time, while IL-10 decreased. IL-1β, IL-1RA, IL-6, TNF-α, and PDGF-bb levels negatively correlated with serum vitamin D. TNF-α levels positively correlated with post-contrast-enhancing brain lesions. IL-15 levels negatively correlated with T2 and Gd(+) lesions in C-spine MRI, while TNF-α, PDGF-bb, and FGF-basic correlated positively with T2 lesions in C-spine MRI. IL-6 levels positively correlated with post-contrast-enhancing lesions in Th-spine MRI. Distinct cytokine profiles in the CSF of de novo diagnosed MS patients provide insights into MS pathogenesis and guide immunomodulatory therapy strategies. Full article
(This article belongs to the Special Issue Challenges and Innovation in Neurodegenerative Diseases)
13 pages, 1375 KiB  
Article
Matrix Remodeling Enzymes as Potential Fluid Biomarkers of Neurodegeneration in Alzheimer’s Disease
by Jelena Bašić, Vuk Milošević, Branka Djordjević, Vladana Stojiljković, Milica Živanović, Nikola Stefanović, Aleksandra Aracki Trenkić, Dragan Stojanov, Tatjana Jevtović Stoimenov and Ivana Stojanović
Int. J. Mol. Sci. 2024, 25(11), 5703; https://doi.org/10.3390/ijms25115703 - 24 May 2024
Viewed by 1003
Abstract
This study investigated the diagnostic accuracy of plasma biomarkers—specifically, matrix metalloproteinase (MMP-9), tissue inhibitor of metalloproteinase (TIMP-1), CD147, and the MMP-/TIMP-1 ratio in patients with Alzheimer’s disease (AD) dementia. The research cohort comprised patients diagnosed with probable AD dementia and a control group [...] Read more.
This study investigated the diagnostic accuracy of plasma biomarkers—specifically, matrix metalloproteinase (MMP-9), tissue inhibitor of metalloproteinase (TIMP-1), CD147, and the MMP-/TIMP-1 ratio in patients with Alzheimer’s disease (AD) dementia. The research cohort comprised patients diagnosed with probable AD dementia and a control group of cognitively unimpaired (CU) individuals. Neuroradiological assessments included brain magnetic resonance imaging (MRI) following dementia protocols, with subsequent volumetric analysis. Additionally, cerebrospinal fluid (CSF) AD biomarkers were classified using the A/T/N system, and apolipoprotein E (APOE) ε4 carrier status was determined. Findings revealed elevated plasma levels of MMP-9 and TIMP-1 in AD dementia patients compared to CU individuals. Receiver operating characteristic (ROC) curve analysis demonstrated significant differences in the areas under the curve (AUC) for MMP-9 (p < 0.001) and TIMP-1 (p < 0.001). Notably, plasma TIMP-1 levels were significantly lower in APOE ε4+ patients than in APOE ε4− patients (p = 0.041). Furthermore, APOE ε4+ patients exhibited reduced hippocampal volume, particularly in total, right, and left hippocampal measurements. TIMP-1 levels exhibited a positive correlation, while the MMP-9/TIMP-1 ratio showed a negative correlation with hippocampal volume parameters. This study sheds light on the potential use of TIMP-1 as a diagnostic marker and its association with hippocampal changes in AD. Full article
(This article belongs to the Special Issue Challenges and Innovation in Neurodegenerative Diseases)
►▼ Show Figures

Figure 1

15 pages, 3582 KiB  
Article
Structurally and Morphologically Distinct Pathological Tau Assemblies Differentially Affect GVB Accumulation
by Marta Jorge-Oliva, Jan R. T. van Weering and Wiep Scheper
Int. J. Mol. Sci. 2023, 24(13), 10865; https://doi.org/10.3390/ijms241310865 - 29 Jun 2023
Cited by 1 | Viewed by 1371
Abstract
Tau aggregation is central to the pathogenesis of a large group of neurodegenerative diseases termed tauopathies, but it is still unclear in which way neurons respond to tau pathology and how tau accumulation leads to neurodegeneration. A striking neuron-specific response to tau pathology [...] Read more.
Tau aggregation is central to the pathogenesis of a large group of neurodegenerative diseases termed tauopathies, but it is still unclear in which way neurons respond to tau pathology and how tau accumulation leads to neurodegeneration. A striking neuron-specific response to tau pathology is presented by granulovacuolar degeneration bodies (GVBs), lysosomal structures that accumulate specific cargo in a dense core. Here we employed different tau aggregation models in primary neurons to investigate which properties of pathological tau assemblies affect GVB accumulation using a combination of confocal microscopy, transmission electron microscopy, and quantitative automated high-content microscopy. Employing GFP-tagged and untagged tau variants that spontaneously form intraneuronal aggregates, we induced pathological tau assemblies with a distinct subcellular localization, morphology, and ultrastructure depending on the presence or absence of the GFP tag. The quantification of the GVB load in the different models showed that an increased GVB accumulation is associated with the untagged tau aggregation model, characterized by shorter and more randomly distributed tau filaments in the neuronal soma. Our data indicate that tau aggregate structure and/or subcellular localization may be key determinants of GVB accumulation. Full article
(This article belongs to the Special Issue Challenges and Innovation in Neurodegenerative Diseases)
►▼ Show Figures

Figure 1

16 pages, 2658 KiB  
Article
Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain Injury
by Wai Hang Cheng, Honor Cheung, Amy Kang, Jianjia Fan, Jennifer Cooper, Mehwish Anwer, Carlos Barron, Anna Wilkinson, Grace Hu, Jefferey Yue, Peter A. Cripton, David J. Vocadlo and Cheryl L. Wellington
Int. J. Mol. Sci. 2023, 24(11), 9439; https://doi.org/10.3390/ijms24119439 - 29 May 2023
Cited by 2 | Viewed by 2097
Abstract
Traumatic brain injury (TBI) is an established risk factor for neurodegenerative diseases. In this study, we used the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) to investigate the effects of a single high-energy TBI in rTg4510 mice, a mouse model of [...] Read more.
Traumatic brain injury (TBI) is an established risk factor for neurodegenerative diseases. In this study, we used the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) to investigate the effects of a single high-energy TBI in rTg4510 mice, a mouse model of tauopathy. Fifteen male rTg4510 mice (4 mo) were impacted at 4.0 J using interfaced CHIMERA and were compared to sham controls. Immediately after injury, the TBI mice showed significant mortality (7/15; 47%) and a prolonged duration of loss of the righting reflex. At 2 mo post-injury, surviving mice displayed significant microgliosis (Iba1) and axonal injury (Neurosilver). Western blotting indicated a reduced p-GSK-3β (S9):GSK-3β ratio in TBI mice, suggesting chronic activation of tau kinase. Although longitudinal analysis of plasma total tau suggested that TBI accelerates the appearance of tau in the circulation, there were no significant differences in brain total or p-tau levels, nor did we observe evidence of enhanced neurodegeneration in TBI mice compared to sham mice. In summary, we showed that a single high-energy head impact induces chronic white matter injury and altered GSK-3β activity without an apparent change in post-injury tauopathy in rTg4510 mice. Full article
(This article belongs to the Special Issue Challenges and Innovation in Neurodegenerative Diseases)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

34 pages, 3216 KiB  
Review
Ferroptosis—A Shared Mechanism for Parkinson’s Disease and Type 2 Diabetes
by Carmen Duță, Corina Muscurel, Carmen Beatrice Dogaru and Irina Stoian
Int. J. Mol. Sci. 2024, 25(16), 8838; https://doi.org/10.3390/ijms25168838 - 14 Aug 2024
Viewed by 1134
Abstract
Type 2 diabetes (T2D) and Parkinson’s disease (PD) are the two most frequent age-related chronic diseases. There are many similarities between the two diseases: both are chronic diseases; both are the result of a decrease in a specific substance—insulin in T2D and dopamine [...] Read more.
Type 2 diabetes (T2D) and Parkinson’s disease (PD) are the two most frequent age-related chronic diseases. There are many similarities between the two diseases: both are chronic diseases; both are the result of a decrease in a specific substance—insulin in T2D and dopamine in PD; and both are caused by the destruction of specific cells—beta pancreatic cells in T2D and dopaminergic neurons in PD. Recent epidemiological and experimental studies have found that there are common underlying mechanisms in the pathophysiology of T2D and PD: chronic inflammation, mitochondrial dysfunction, impaired protein handling and ferroptosis. Epidemiological research has indicated that there is a higher risk of PD in individuals with T2D. Moreover, clinical studies have observed that the symptoms of Parkinson’s disease worsen significantly after the onset of T2D. This article provides an up-to-date review on the intricate interplay between oxidative stress, reactive oxygen species (ROS) and ferroptosis in PD and T2D. By understanding the shared molecular pathways and how they can be modulated, we can develop more effective therapies, or we can repurpose existing drugs to improve patient outcomes in both disorders. Full article
(This article belongs to the Special Issue Challenges and Innovation in Neurodegenerative Diseases)
►▼ Show Figures

Figure 1

13 pages, 606 KiB  
Review
Nervonic Acid Synthesis Substrates as Essential Components in Profiled Lipid Supplementation for More Effective Central Nervous System Regeneration
by Magdalena Namiecinska, Paweł Piatek and Przemysław Lewkowicz
Int. J. Mol. Sci. 2024, 25(7), 3792; https://doi.org/10.3390/ijms25073792 - 28 Mar 2024
Cited by 2 | Viewed by 1675
Abstract
Central nervous system (CNS) damage leads to severe neurological dysfunction as a result of neuronal cell death and axonal degeneration. As, in the mature CNS, neurons have little ability to regenerate their axons and reconstruct neural loss, demyelination is one of the hallmarks [...] Read more.
Central nervous system (CNS) damage leads to severe neurological dysfunction as a result of neuronal cell death and axonal degeneration. As, in the mature CNS, neurons have little ability to regenerate their axons and reconstruct neural loss, demyelination is one of the hallmarks of neurological disorders such as multiple sclerosis (MS). Unfortunately, remyelination, as a regenerative process, is often insufficient to prevent axonal loss and improve neurological deficits after demyelination. Currently, there are still no effective therapeutic tools to restore neurological function, but interestingly, emerging studies prove the beneficial effects of lipid supplementation in a wide variety of pathological processes in the human body. In the future, available lipids with a proven beneficial effect on CNS regeneration could be included in supportive therapy, but this topic still requires further studies. Based on our and others’ research, we review the role of exogenous lipids, pointing to substrates that are crucial in the remyelination process but are omitted in available studies, justifying the properly profiled supply of lipids in the human diet as a supportive therapy during CNS regeneration. Full article
(This article belongs to the Special Issue Challenges and Innovation in Neurodegenerative Diseases)
►▼ Show Figures

Graphical abstract

13 pages, 958 KiB  
Review
Hypoxia Sensing and Responses in Parkinson’s Disease
by Johannes Burtscher, Yves Duderstadt, Hannes Gatterer, Martin Burtscher, Roman Vozdek, Grégoire P. Millet, Andrew A. Hicks, Hannelore Ehrenreich and Martin Kopp
Int. J. Mol. Sci. 2024, 25(3), 1759; https://doi.org/10.3390/ijms25031759 - 1 Feb 2024
Cited by 3 | Viewed by 2477
Abstract
Parkinson’s disease (PD) is associated with various deficits in sensing and responding to reductions in oxygen availability (hypoxia). Here we summarize the evidence pointing to a central role of hypoxia in PD, discuss the relation of hypoxia and oxygen dependence with pathological hallmarks [...] Read more.
Parkinson’s disease (PD) is associated with various deficits in sensing and responding to reductions in oxygen availability (hypoxia). Here we summarize the evidence pointing to a central role of hypoxia in PD, discuss the relation of hypoxia and oxygen dependence with pathological hallmarks of PD, including mitochondrial dysfunction, dopaminergic vulnerability, and alpha-synuclein-related pathology, and highlight the link with cellular and systemic oxygen sensing. We describe cases suggesting that hypoxia may trigger Parkinsonian symptoms but also emphasize that the endogenous systems that protect from hypoxia can be harnessed to protect from PD. Finally, we provide examples of preclinical and clinical research substantiating this potential. Full article
(This article belongs to the Special Issue Challenges and Innovation in Neurodegenerative Diseases)
►▼ Show Figures

Figure 1

29 pages, 2484 KiB  
Review
Control Theory and Systems Biology: Potential Applications in Neurodegeneration and Search for Therapeutic Targets
by Andrea Angarita-Rodríguez, Yeimy González-Giraldo, Juan J. Rubio-Mesa, Andrés Felipe Aristizábal, Andrés Pinzón and Janneth González
Int. J. Mol. Sci. 2024, 25(1), 365; https://doi.org/10.3390/ijms25010365 - 27 Dec 2023
Viewed by 2309
Abstract
Control theory, a well-established discipline in engineering and mathematics, has found novel applications in systems biology. This interdisciplinary approach leverages the principles of feedback control and regulation to gain insights into the complex dynamics of cellular and molecular networks underlying chronic diseases, including [...] Read more.
Control theory, a well-established discipline in engineering and mathematics, has found novel applications in systems biology. This interdisciplinary approach leverages the principles of feedback control and regulation to gain insights into the complex dynamics of cellular and molecular networks underlying chronic diseases, including neurodegeneration. By modeling and analyzing these intricate systems, control theory provides a framework to understand the pathophysiology and identify potential therapeutic targets. Therefore, this review examines the most widely used control methods in conjunction with genomic-scale metabolic models in the steady state of the multi-omics type. According to our research, this approach involves integrating experimental data, mathematical modeling, and computational analyses to simulate and control complex biological systems. In this review, we find that the most significant application of this methodology is associated with cancer, leaving a lack of knowledge in neurodegenerative models. However, this methodology, mainly associated with the Minimal Dominant Set (MDS), has provided a starting point for identifying therapeutic targets for drug development and personalized treatment strategies, paving the way for more effective therapies. Full article
(This article belongs to the Special Issue Challenges and Innovation in Neurodegenerative Diseases)
►▼ Show Figures

Figure 1

33 pages, 2200 KiB  
Review
Exploring the Potential of Aptamers in Targeting Neuroinflammation and Neurodegenerative Disorders: Opportunities and Challenges
by Anna Hau-Yee Kong, Aston Jiaxi Wu, Olivia Ka-Yi Ho, Maggie Ming-Ki Leung, Alexis Shiying Huang, Yuanyuan Yu, Ge Zhang, Aiping Lyu, Min Li and King-Ho Cheung
Int. J. Mol. Sci. 2023, 24(14), 11780; https://doi.org/10.3390/ijms241411780 - 22 Jul 2023
Cited by 5 | Viewed by 3018
Abstract
Neuroinflammation is the precursor for several neurodegenerative diseases (NDDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Targeting neuroinflammation has emerged as a promising strategy to address a wide range of CNS pathologies. These NDDs still present significant challenges [...] Read more.
Neuroinflammation is the precursor for several neurodegenerative diseases (NDDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Targeting neuroinflammation has emerged as a promising strategy to address a wide range of CNS pathologies. These NDDs still present significant challenges in terms of limited and ineffective diagnosis and treatment options, driving the need to explore innovative and novel therapeutic alternatives. Aptamers are single-stranded nucleic acids that offer the potential for addressing these challenges through diagnostic and therapeutic applications. In this review, we summarize diagnostic and therapeutic aptamers for inflammatory biomolecules, as well as the inflammatory cells in NDDs. We also discussed the potential of short nucleotides for Aptamer-Based Targeted Brain Delivery through their unique features and modifications, as well as their ability to penetrate the blood-brain barrier. Moreover, the unprecedented opportunities and substantial challenges of using aptamers as therapeutic agents, such as drug efficacy, safety considerations, and pharmacokinetics, are also discussed. Taken together, this review assesses the potential of aptamers as a pioneering approach for target delivery to the CNS and the treatment of neuroinflammation and NDDs. Full article
(This article belongs to the Special Issue Challenges and Innovation in Neurodegenerative Diseases)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-9
Back to TopTop