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Biomarkers in Neoplastic and Degenerative CNS Diseases: Defining New Advances in Clinical Usefulness and Therapeutic Molecular Target

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 (31 July 2024) | Viewed by 5232

Special Issue Editor

Dr. Giulia Bivona

E-Mail Website
Guest Editor
Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy
Interests: laboratory medicine; vitamin D; biomarkers; neurodegeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The search for biomarkers in neurodegenerative disease and central nervous system (CNS) cancer has become a high-interest research field in recent decades, attracting great attention from scientists worldwide.

Well-established molecules have been documented to display clinical usefulness in neurodegenerative diseases, as these have an impact on clinical practice, enabling diagnosis and prognosis and predicting therapy response. However, many concerns still remain about the use of some biomarkers, with many issues needing to be overcome. For instance, Alzheimer’s disease (AD) only benefits from cerebrospinal fluid-validated biomarkers, which unfortunately display some flaws: high costs, no serial repeatability and invasive procedures to collect samples. Also, despite many insights on the pathophysiology of AD, no biomarkers have been identified to be used as a valuable molecular target for disease-modifying treatment.

CNS cancer is currently diagnosed using expensive, time-consuming and invasive tools, including imaging and histochemical ones, with rare cases of blood biomarkers with established clinical usefulness. Hence, there is an urgent need for biomarkers to be detected using easy-to-collect fluids and low-cost, rapid instrumentations and methodologies.

This Special Issue aims to collect research articles on novel, reliable biomarkers for CNS neurodegenerative and neoplastic diseases in order to identify valuable molecules to be validated and used in clinical practice. Also, studies on molecules that can be used as therapeutic targets are encouraged. Papers reporting new methodologies for biomarkers’ measurement are welcome as well, along with review articles summarizing novel findings on this topic.

Dr. Giulia Bivona
Guest Editor

Manuscript Submission Information

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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.

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Keywords

  • Alzheimer’s disease
  • brain cancer
  • clinical usefulness
  • therapeutic target

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Published Papers (3 papers)

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Research

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18 pages, 2352 KiB  
Article
Neurodegeneration Biomarkers in Adult Spinal Muscular Atrophy (SMA) Patients Treated with Nusinersen
by Pol Andrés-Benito, Juan Francisco Vázquez-Costa, Nancy Carolina Ñungo Garzón, María J. Colomina, Carla Marco, Laura González, Cristina Terrafeta, Raúl Domínguez, Isidro Ferrer and Mónica Povedano
Int. J. Mol. Sci. 2024, 25(7), 3810; https://doi.org/10.3390/ijms25073810 - 29 Mar 2024
Cited by 1 | Viewed by 1792
Abstract
The objective of this study is to evaluate biomarkers for neurodegenerative disorders in adult SMA patients and their potential for monitoring the response to nusinersen. Biomarkers for neurodegenerative disorders were assessed in plasma and CSF samples obtained from a total of 30 healthy [...] Read more.
The objective of this study is to evaluate biomarkers for neurodegenerative disorders in adult SMA patients and their potential for monitoring the response to nusinersen. Biomarkers for neurodegenerative disorders were assessed in plasma and CSF samples obtained from a total of 30 healthy older adult controls and 31 patients with adult SMA type 2 and 3. The samples were collected before and during nusinersen treatment at various time points, approximately at 2, 6, 10, and 22 months. Using ELISA technology, the levels of total tau, pNF-H, NF-L, sAPPβ, Aβ40, Aβ42, and YKL-40 were evaluated in CSF samples. Additionally, plasma samples were used to measure NF-L and total tau levels using SIMOA technology. SMA patients showed improvements in clinical outcomes after nusinersen treatment, which were statistically significant only in walkers, in RULM (p = 0.04) and HFMSE (p = 0.05) at 24 months. A reduction in sAPPβ levels was found after nusinersen treatment, but these levels did not correlate with clinical outcomes. Other neurodegeneration biomarkers (NF-L, pNF-H, total tau, YKL-40, Aβ40, and Aβ42) were not found consistently changed with nusinersen treatment. The slow progression rate and mild treatment response of adult SMA types 2 and 3 may not lead to detectable changes in common markers of axonal degradation, inflammation, or neurodegeneration, since it does not involve large pools of damaged neurons as observed in pediatric forms. However, changes in biomarkers associated with the APP processing pathway might be linked to treatment administration. Further studies are warranted to better understand these findings. Full article
(This article belongs to the Special Issue Biomarkers in Neoplastic and Degenerative CNS Diseases: Defining New Advances in Clinical Usefulness and Therapeutic Molecular Target)
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Review

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24 pages, 1262 KiB  
Review
The Role of α-Synuclein in Etiology of Neurodegenerative Diseases
by Daria Krawczuk, Magdalena Groblewska, Jan Mroczko, Izabela Winkel and Barbara Mroczko
Int. J. Mol. Sci. 2024, 25(17), 9197; https://doi.org/10.3390/ijms25179197 - 24 Aug 2024
Viewed by 1092
Abstract
A presynaptic protein called α-synuclein plays a crucial role in synaptic function and neurotransmitter release. However, its misfolding and aggregation have been implicated in a variety of neurodegenerative diseases, particularly Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Emerging evidence suggests [...] Read more.
A presynaptic protein called α-synuclein plays a crucial role in synaptic function and neurotransmitter release. However, its misfolding and aggregation have been implicated in a variety of neurodegenerative diseases, particularly Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Emerging evidence suggests that α-synuclein interacts with various cellular pathways, including mitochondrial dysfunction, oxidative stress, and neuroinflammation, which contributes to neuronal cell death. Moreover, α-synuclein has been involved in the propagation of neurodegenerative processes through prion-like mechanisms, where misfolded proteins induce similar conformational changes in neighboring neurons. Understanding the multifaced roles of α-synuclein in neurodegeneration not only aids in acquiring more knowledge about the pathophysiology of these diseases but also highlights potential biomarkers and therapeutic targets for intervention in alpha-synucleinopathies. In this review, we provide a summary of the mechanisms by which α-synuclein contributes to neurodegenerative processes, focusing on its misfolding, oligomerization, and the formation of insoluble fibrils that form characteristic Lewy bodies. Furthermore, we compare the potential value of α-synuclein species in diagnosing and differentiating selected neurodegenerative diseases. Full article
(This article belongs to the Special Issue Biomarkers in Neoplastic and Degenerative CNS Diseases: Defining New Advances in Clinical Usefulness and Therapeutic Molecular Target)
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13 pages, 284 KiB  
Review
Nucleic Acids-Based Biomarkers for Alzheimer’s Disease Diagnosis and Novel Molecules to Treat the Disease
by Giulia Bivona, Selene Sammataro and Giulio Ghersi
Int. J. Mol. Sci. 2024, 25(14), 7893; https://doi.org/10.3390/ijms25147893 - 19 Jul 2024
Viewed by 1713
Abstract
Alzheimer’s disease (AD) represents the most common form of dementia and affects million people worldwide, with a high social burden and considerable economic costs. AD diagnosis benefits from a well-established panel of laboratory tests that allow ruling-in patients, along with FDG and amyloid [...] Read more.
Alzheimer’s disease (AD) represents the most common form of dementia and affects million people worldwide, with a high social burden and considerable economic costs. AD diagnosis benefits from a well-established panel of laboratory tests that allow ruling-in patients, along with FDG and amyloid PET imaging tools. The main laboratory tests used to identify AD patients are Aβ40, Aβ42, the Aβ42/Aβ40 ratio, phosphorylated Tau 181 (pTau181) and total Tau (tTau). Although they are measured preferentially in the cerebrospinal fluid (CSF), some evidence about the possibility for blood-based determination to enter clinical practice is growing up. Unfortunately, CSF biomarkers for AD and, even more, the blood-based ones, present a few flaws, and twenty years of research in this field did not overcome these pitfalls. The tale even worsens when the issue of treating AD is addressed due to the lack of effective strategies despite the many decades of attempts by pharmaceutic industries and scientists. Amyloid-based drugs failed to stop the disease, and no neuroinflammation-based drugs have been demonstrated to work so far. Hence, only symptomatic therapy is available, with no disease-modifying treatment on hand. Such a desolate situation fully justifies the active search for novel biomarkers to be used as reliable tests for AD diagnosis and molecular targets for treating patients. Recently, a novel group of molecules has been identified to be used for AD diagnosis and follow-up, the nuclei acid-based biomarkers. Nucleic acid-based biomarkers are a composite group of extracellular molecules consisting of DNA and RNA alone or in combination with other molecules, including proteins. This review article reports the main findings from the studies carried out on these biomarkers during AD, and highlights their advantages and limitations. Full article
(This article belongs to the Special Issue Biomarkers in Neoplastic and Degenerative CNS Diseases: Defining New Advances in Clinical Usefulness and Therapeutic Molecular Target)
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