Molecular Mechanisms in Neurodegenerative Diseases: Clinical and Therapeutic Perspectives—Volume II

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: 15 April 2025 | Viewed by 868

Special Issue Editors


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Guest Editor
ALS Centre, Neurology Unit, Maggiore della Carità University Hospital, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
Interests: neurodegeneration; amyotrophic lateral sclerosis; biomarkers; genetics
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Guest Editor
1. Neurology Unit, S. Andrea Hospital, Department of Translational Medicine, University of Piemonte Orientale, Vercelli, Italy
2. In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
Interests: dementia; mild cognitive impairment; biomarkers; neurodegeneration; PET imaging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurodegenerative diseases are progressive and debilitating conditions that result in inexorable neural degeneration and loss. To date, none of the existing therapeutic strategies can effectively stop or modify the pathological processes leading to neurodegeneration.

In recent decades, researchers have been trying to enhance the development of reliable biomarkers for neurodegenerative diseases, while medical practice has been moving toward precision medicine. However, there is still an urgent need to identify disease-specific biomarkers to improve the early diagnostic workup, favor clinical classification and prognostic models, and facilitate the development of effective disease-modifying therapies. Most neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, are characterized by the abnormal deposition of misfolded proteins in the central nervous system, resulting in neuronal degeneration and ultimately neuronal damage death. Several environmental factors have been proposed to contribute to neuronal damage and degenerative changes, and the genetic profile may also prepare the pathophysiological process underlying neurodegeneration. Distinct molecular and functional pathways may become dysregulated, including neurophysiology feedbacks, long-distance brain network organization, and neuroinflammatory responses. Pathology alterations can be detected, in vivo, by searching for cerebrospinal fluid alterations or using positron emission tomography to detect abnormal protein accumulation. Brain imaging can also reveal functional and molecular connectivity changes, and neurophysiology techniques may track additional early disease-specific dysfunctions. Genetic profiling can aid the identification of possible clinical trajectories along the neurodegenerative process, offering the possibility to test therapeutic strategies in a pre-symptomatic phase. Similarly, the investigation of neuroinflammatory responses represents a possible invaluable tool in monitoring disease progression and predicting clinical outcomes.

This Special Issue aims to highlight the current knowledge regarding neurodegeneration pathogenic mechanisms and underline possible diagnostic and therapeutic repercussions in neurodegenerative diseases.

In this Special Issue, original articles and reviews are welcome. We look forward to receiving your contributions.

Dr. Fabiola De Marchi
Dr. Giacomo Tondo
Guest Editors

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Keywords

  • neurodegeneration
  • aging
  • dementia
  • motoneuron disease
  • movement disorders
  • precision medicine
  • biomarkers

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Published Papers (1 paper)

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Research

16 pages, 533 KiB  
Article
SMN2 Copy Number Association with Spinal Muscular Atrophy Severity: Insights from Colombian Patients
by José Lamadrid-González, Sandra Castellar-Leones, Julio César Contreras-Velásquez and Valmore Bermúdez
J. Clin. Med. 2024, 13(21), 6402; https://doi.org/10.3390/jcm13216402 - 25 Oct 2024
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Abstract
Background: Spinal muscular atrophy (SMA) is a genetic neurodegenerative disease primarily affecting paediatric patients, often leading to significant morbidity and mortality. Our principal objective is to describe the sociodemographic characteristics and evaluate the association between the number of SMN2 copies and SMA type [...] Read more.
Background: Spinal muscular atrophy (SMA) is a genetic neurodegenerative disease primarily affecting paediatric patients, often leading to significant morbidity and mortality. Our principal objective is to describe the sociodemographic characteristics and evaluate the association between the number of SMN2 copies and SMA type in patients from the Colombian Foundation for Spinal Muscular Atrophy (FAMECOL) database. Methodology: An analytical cross-sectional study was conducted on 201 patients with a genetic diagnosis of SMA. Data were identified, extracted, and collected from patient records provided by FAMECOL as patients registered with the association, including 201 patients from April 2013 to April 2024, when the database was delivered. Qualitative variables were described using relative and absolute frequencies, while quantitative variables were described using central tendency and dispersion measures according to their distribution. The association between the SMA type and the SMN2 number of copies was assessed by Fisher’s exact test (1 to 5 copies). Results: Of the 201 patients studied, 42% were female (n = 85), and 58% were male (n = 116). The median age was 9 years (IQR 4–16 years). The median age at diagnosis was 9 years (IQR 4–16), varying by subgroup: 2, 7, 14, and 41.5 years for each type, respectively. A total of 25% patients were from Antioquia (n = 51). Eighty-nine per cent had gastrostomy (n = 18). The association between the two variables was statistically significant (p < 0.05). Conclusion: This study highlights SMA clinical variability and its association with the number of SMN2 copies, underscoring the importance of a personalised approach to diagnosing and managing this disease. The findings may guide more effective therapeutic strategies to improve patients’ quality of life. Full article
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