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Mechanisms and Novel Therapeutic Approaches for Neurodegenerative Diseases

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 4836

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Special Issue Editor

Dr. Fernando Cardona

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Guest Editor

Instituto de Biomedicina de Valencia-CSIC, 46010 Valencia, Spain
Interests: genetics; molecular biology; biochemistry; neurodegenerative diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurodegenerative Diseases are among the main health problems in elderly. These pathologies generate autonomy problems in the affected people, as well as important public health problems and an important cost for the health systems.

The mechanisms underlying neurodegeneration are sometimes common to various diseases, and differentiated in other cases. In any case, in many cases the mechanisms are unknown, and in others, despite being known, there are no effective therapies to treat these diseases. In fact, there are few therapies for the treatment of these diseases, and either for preventing, slowing or stopping neurodegeneration.

In this Special Issue, we invite our colleagues to send review and original research articles that focus on any aspect of molecular and cellular mechanisms of neurodegeneration, as well as therapeutic approaches. Also manuscripts dealing with related subjects will be appreciated.

Dr. Fernando Cardona
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. Biomedicines 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 2600 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

neurodegenerative diseases
cellular mechanisms
molecular mechanisms
neurodegeneration models
protein misfolding
protein aggregation
neuronal death
molecular therapy
cellular therapy
therapeutics
medical chemistry
drug screening

Published Papers (4 papers)

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Research

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18 pages, 4058 KiB

Open AccessArticle

Combined Metabolic Activators with Different NAD+ Precursors Improve Metabolic Functions in the Animal Models of Neurodegenerative Diseases

by Ozlem Altay, Hong Yang, Serkan Yildirim, Cemil Bayram, Ismail Bolat, Sena Oner, Ozlem Ozdemir Tozlu, Mehmet Enes Arslan, Ahmet Hacimuftuoglu, Saeed Shoaie, Cheng Zhang, Jan Borén, Mathias Uhlén, Hasan Turkez and Adil Mardinoglu

Biomedicines 2024, 12(4), 927; https://doi.org/10.3390/biomedicines12040927 - 22 Apr 2024

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Abstract

Background: Mitochondrial dysfunction and metabolic abnormalities are acknowledged as significant factors in the onset of neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Our research has demonstrated that the use of combined metabolic activators (CMA) may alleviate metabolic dysfunctions and stimulate mitochondrial metabolism. Therefore, the use of CMA could potentially be an effective therapeutic strategy to slow down or halt the progression of PD and AD. CMAs include substances such as the glutathione precursors (L-serine and N-acetyl cysteine), the NAD+ precursor (nicotinamide riboside), and L-carnitine tartrate. Methods: Here, we tested the effect of two different formulations, including CMA1 (nicotinamide riboside, L-serine, N-acetyl cysteine, L-carnitine tartrate), and CMA2 (nicotinamide, L-serine, N-acetyl cysteine, L-carnitine tartrate), as well as their individual components, on the animal models of AD and PD. We assessed the brain and liver tissues for pathological changes and immunohistochemical markers. Additionally, in the case of PD, we performed behavioral tests and measured responses to apomorphine-induced rotations. Findings: Histological analysis showed that the administration of both CMA1 and CMA2 formulations led to improvements in hyperemia, degeneration, and necrosis in neurons for both AD and PD models. Moreover, the administration of CMA2 showed a superior effect compared to CMA1. This was further corroborated by immunohistochemical data, which indicated a reduction in immunoreactivity in the neurons. Additionally, notable metabolic enhancements in liver tissues were observed using both formulations. In PD rat models, the administration of both formulations positively influenced the behavioral functions of the animals. Interpretation: Our findings suggest that the administration of both CMA1 and CMA2 markedly enhanced metabolic and behavioral outcomes, aligning with neuro-histological observations. These findings underscore the promise of CMA2 administration as an effective therapeutic strategy for enhancing metabolic parameters and cognitive function in AD and PD patients. Full article

(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Neurodegenerative Diseases)

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11 pages, 2104 KiB

Open AccessArticle

UBL3 Interaction with α-Synuclein Is Downregulated by Silencing MGST3

by Jing Yan, Hengsen Zhang, Yuna Tomochika, Bin Chen, Yashuang Ping, Md. Shoriful Islam, Shuhei Aramaki, Tomohito Sato, Yu Nagashima, Tomohiko Nakamura, Tomoaki Kahyo, Daita Kaneda, Kenji Ogawa, Minoru Yoshida and Mitsutoshi Setou

Biomedicines 2023, 11(9), 2491; https://doi.org/10.3390/biomedicines11092491 - 08 Sep 2023

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Abstract

Ubiquitin-like 3 (UBL3) is a membrane-anchored protein that plays a crucial role in sorting proteins into small extracellular vesicles. Aggregations of alpha-synuclein (α-syn) are associated with the pathology of neurodegenerative diseases such as Parkinson’s disease. Recently, the interaction between UBL3 and α-syn was discovered, with potential implications in clearing excess α-syn from neurons and its role in disease spread. However, the regulator that can mediate the interaction between UBL3 and α-syn remains unclear. In this study, using the split gaussian luciferase complementation assay and RNA interference technology, we identified that QSOX2, HTATIP2, UBE3C, MGST3, NSF, HECTD1, SAE1, and ATG3 were involved in downregulating the interaction between UBL3 and α-syn. Notably, silencing MGST3 had the most significant impact. Immunocytochemistry staining confirmed the impact of MGST3 silencing on the co-localization of UBL3 and α-syn in cells. MGST3 is a part of the antioxidant system, and silencing MGST3 is believed to contribute to oxidative stress. We induced oxidative stress with hydrogen peroxide, observing its effect on the UBL3-α-syn interaction, and showing that 800 µM of H₂O₂ downregulated this interaction. In conclusion, silencing MGST3 downregulates the interaction between UBL3 and α-syn. Full article

(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Neurodegenerative Diseases)

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Review

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64 pages, 2125 KiB

Open AccessReview

Co-Culture Models: Key Players in In Vitro Neurotoxicity, Neurodegeneration and BBB Modeling Studies

by Ana Rita Monteiro, Daniel José Barbosa, Fernando Remião and Renata Silva

Biomedicines 2024, 12(3), 626; https://doi.org/10.3390/biomedicines12030626 - 12 Mar 2024

Viewed by 827

Abstract

The biological barriers existing in the human body separate the blood circulation from the interstitial fluid in tissues. The blood–brain barrier (BBB) isolates the central nervous system from the bloodstream, presenting a dual role: the protection of the human brain against potentially toxic/harmful substances coming from the blood, while providing nutrients to the brain and removing metabolites. In terms of architectural features, the presence of junctional proteins (that restrict the paracellular transport) and the existence of efflux transporters at the BBB are the two major in vivo characteristics that increase the difficulty in creating an ideal in vitro model for drug permeability studies and neurotoxicity assessments. The purpose of this work is to provide an up-to-date literature review on the current in vitro models used for BBB studies, focusing on the characteristics, advantages, and disadvantages of both primary cultures and immortalized cell lines. An accurate analysis of the more recent and emerging techniques implemented to optimize the in vitro models is also provided, based on the need of recreating as closely as possible the BBB microenvironment. In fact, the acceptance that the BBB phenotype is much more than endothelial cells in a monolayer has led to the shift from single-cell to multicellular models. Thus, in vitro co-culture models have narrowed the gap between recreating as faithfully as possible the human BBB phenotype. This is relevant for permeability and neurotoxicity assays, and for studies related to neurodegenerative diseases. Several studies with these purposes will be also presented and discussed. Full article

(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Neurodegenerative Diseases)

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17 pages, 795 KiB

Open AccessReview

Some Novel Therapies in Parkinson’s Disease: A Promising Path Forward or Not Yet? A Systematic Review of the Literature

by Anastasia Bougea

Biomedicines 2024, 12(3), 549; https://doi.org/10.3390/biomedicines12030549 - 29 Feb 2024

Viewed by 1343

Abstract

In light of the unsuccessful traditional therapies for Parkinson’s disease (PD) overmany years, there is an unmet need for the development of novel therapies to alleviate the symptoms of PD retardation or halt the progression of the disease itself. This systematic review aims to critically update some of the most promising novel treatments including gene therapy, cell-based therapies, targeted drug delivery, and neuroprotective agents, focusing on their challenges, limitations and future directions in PD research. Gene therapy in PD is encouraging, with AAV-based approaches targeting neurotrophic factors, dopamine production, and neuronal circuits in animal and clinical trials. A promising approach to targeted drug delivery for PD involves the use of nanotechnology to create drug delivery vehicles that can traverse the blood–brain barrier and deliver medications specifically to the regions of the brain affected by PD. Neuroprotective agents are compounds that have the ability to protect neurons from degeneration and death, and they hold great promise for the evolution of disease-modifying treatments for PD. Magnetic field therapy is a promising non-invasive method that promotes neural plasticity in PD. The establishment of standardized protocols for animal and human studies, safety, ethical considerations, and cost-effectiveness are the major challenges for the future research of novel PD therapies. The development of novel therapies for PD represents a promising path toward to effective personalized disease-modifying treatments for PD. Full article

(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Neurodegenerative Diseases)

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