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New Challenges of Parkinson’s Disease
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New Challenges of Parkinson’s Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 25 June 2024 | Viewed by 4826

Special Issue Editors

Dr. Cristina Agliardi

E-Mail Website
Guest Editor
IRCCS Fondazione Don Carlo Gnocchi, 20147 Milan, Italy
Interests: extracellular vesicles; neurodegenerative disorders
Dr. Franca R. Guerini

E-Mail Website
Guest Editor
Laboratory of Molecular Medicine and Biotechnology, IRCCS Fondazione Don Carlo Gnocchi, Via Capecelatro 66, 20148 Milan, Italy
Interests: genetics; autism; neurodegenerative disorders; Alzheimer; multiple sclerosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder characterized by both motor and non-motor symptoms including sleep and mood disorders and cognitive, sensory and autonomic dysfunctions. The etiology of the disease in most patients is unknown, but different genetic causes have been identified. Moreover, the existing treatments are limited in effect and mainly address the symptoms rather than the cause or the progressive course. Improving our understanding of what causes the complexity and diversity of PD is a major challenge for researchers. Tools are needed to group people with similar types of PD so that individuals who are most likely to benefit from clinical trials can be studied and their responses to treatment can be compared in a meaningful way. The aim of this Special Issue is to collect the latest research on PD in terms of:

  • Etiology understanding: genetic and environmental influences, mitochondrial dysfunction, protein aggregation, misfolding and cell-to-cell spreading mechanisms, neuroinflammation, etc.;
  • New biomarkers discovery: imaging scans (MRI, CT), extracellular vesicles in biofluids, genetics, epigenetics and microbiome analysis;
  • Novel disease-modifying treatments: gene therapy, deep brain stimulation and animal models;
  • Strategies that provide symptoms relief: diet, exercise, rehabilitation and stress reduction.

We welcome both original research and review articles.

Dr. Cristina Agliardi
Dr. Franca R. Guerini
Guest Editors

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

  • Parkinson’s disease
  • neurodegeneration
  • synuclein
  • diagnosis
  • genetics
  • epigenetics
  • extracellular vesicles
  • biomarkers
  • treatments
  • rehabilitation
 

Published Papers (4 papers)

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Research

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12 pages, 2981 KiB  
Article
Association between Decreased SGK1 and Increased Intestinal α-Synuclein in an MPTP Mouse Model of Parkinson’s Disease
by Min Hyung Seo, Dasom Kwon, Soo-Hwan Kim and Sujung Yeo
Int. J. Mol. Sci. 2023, 24(22), 16408; https://doi.org/10.3390/ijms242216408 - 16 Nov 2023
Viewed by 782
Abstract
Parkinson’s disease (PD) is a globally common progressive neurodegenerative disease resulting from the loss of dopaminergic neurons in the brain. Increased α-synuclein (α-syn) is associated with the degeneration of dopaminergic neurons and non-motor symptoms like gastrointestinal disorders. In this study, we investigated the [...] Read more.
Parkinson’s disease (PD) is a globally common progressive neurodegenerative disease resulting from the loss of dopaminergic neurons in the brain. Increased α-synuclein (α-syn) is associated with the degeneration of dopaminergic neurons and non-motor symptoms like gastrointestinal disorders. In this study, we investigated the association between serum/glucocorticoid-related kinase 1 (SGK1) and α-syn in the colon of a PD mouse model. SGK1 and α-syn expression patterns were opposite in the surrounding colon tissue, with decreased SGK1 expression and increased α-syn expression in the PD group. Immunofluorescence analyses revealed the colocation of SGK1 and α-syn; the PD group demonstrated weaker SGK1 expression and stronger α-syn expression than the control group. Immunoblotting analysis showed that Na+/K+ pump ATPase α1 expression levels were significantly increased in the PD group. In SW480 cells with SGK1 knockdown using SGK1 siRNA, decreasing SGK1 levels corresponded with significant increases in the expression levels of α-syn and ATPase α1. These results suggest that SGK1 significantly regulates Na+/K+ pump ATPase, influencing the relationship between electrolyte balance and fecal formation in the PD mouse model. Gastrointestinal disorders are some of the major prodromal symptoms of PD. Therefore, modulating SGK1 expression could be an important strategy for controlling PD. Full article
(This article belongs to the Special Issue New Challenges of Parkinson’s Disease)
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10 pages, 1079 KiB  
Article
YKL-40 and the Cellular Metabolic Profile in Parkinson’s Disease
by Maria Gevezova, Maria Kazakova, Anastasia Trenova and Victoria Sarafian
Int. J. Mol. Sci. 2023, 24(22), 16297; https://doi.org/10.3390/ijms242216297 - 14 Nov 2023
Viewed by 843
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. A growing body of evidence suggests that mitochondrial dysfunction and inflammation play a crucial role as a pathogenetic mechanism in PD. The glycoprotein YKL-40 (CHI3L1) is a potential biomarker involved in inflammation [...] Read more.
Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. A growing body of evidence suggests that mitochondrial dysfunction and inflammation play a crucial role as a pathogenetic mechanism in PD. The glycoprotein YKL-40 (CHI3L1) is a potential biomarker involved in inflammation and tumor processes. The aim of the present study was to investigate the metabolic profile of PBMCs from PD patients and to search for a possible relationship between cellular bioenergetics and YKL-40. The study included 18 naïve PD patients and an age-matched control group (HC, n = 7). Patients were diagnosed according to the MDS-PD, the UPDRS, and the Hoen–Yahr scales. Mitochondrial activity was measured by a metabolic analyzer on isolated PBMCs from PD patients. Gene (qPCR) and protein (ELISA) expression levels of YKL40 were investigated. New data are reported revealing changes in the mitochondrial activity and YKL-40 levels in PD patients. Bioenergetic parameters showed increased respiratory reserve capacity in PD compared to HC. The protein levels of YKL-40 were threefold higher in PD. We found a correlation between the YKL-40 protein levels and basal respiration and between YKL-40 and ATP production. These observations suggest an interplay between YKL-40 and mitochondrial function in PD. We assume that the YKL-40 gene and protein levels in combination with changes in mitochondrial function might serve as an additional tool to monitor the clinical course of PD. Full article
(This article belongs to the Special Issue New Challenges of Parkinson’s Disease)
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14 pages, 2264 KiB  
Article
Alpha-Synuclein-Specific Regulatory T Cells Ameliorate Parkinson’s Disease Progression in Mice
by Seon-Young Park, HyeJin Yang, Soyoung Kim, Juwon Yang, Hyemin Go and Hyunsu Bae
Int. J. Mol. Sci. 2023, 24(20), 15237; https://doi.org/10.3390/ijms242015237 - 16 Oct 2023
Cited by 3 | Viewed by 1371
Abstract
Parkinson’s disease (PD) is a long-term neurodegenerative disease characterized by dopaminergic neuronal loss and the aggregation of alpha-synuclein (α-syn) in the brain. Cell therapy using regulatory T cells (Tregs) has therapeutic potential on PD progression in a mouse model; however, several challenges were [...] Read more.
Parkinson’s disease (PD) is a long-term neurodegenerative disease characterized by dopaminergic neuronal loss and the aggregation of alpha-synuclein (α-syn) in the brain. Cell therapy using regulatory T cells (Tregs) has therapeutic potential on PD progression in a mouse model; however, several challenges were associated with its applications. Here, we propose a strategy for α-syn specific Treg expansion (α-syn Treg). We presented α-syn to T cells via dendritic cells. This method increased the mobility of Tregs towards the site of abundant α-syn in vitro (p < 0.01; α-syn Tregs versus polyclonal Tregs (poly Tregs)) and in vivo. Consequently, α-syn Tregs showed noteworthy neuroprotective effects against motor function deficits (p < 0.05, p < 0.01; α-syn Tregs versus poly Tregs), dopaminergic neuronal loss (p < 0.001; α-syn Tregs versus poly Tregs), and α-syn accumulation (p < 0.05; α-syn Tregs versus poly Tregs) in MPTP-induced PD mice. Furthermore, the adoptive transfer of α-syn Tregs exerted immunosuppressive effects on activated microglia, especially pro-inflammatory microglia, in PD mice. Our findings suggest that α-syn presentation may provide a significant improvement in neuroprotective activities of Tregs and suggest the effective clinical application of Treg therapy in PD. Full article
(This article belongs to the Special Issue New Challenges of Parkinson’s Disease)
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Review

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18 pages, 571 KiB  
Review
Extracellular Vesicles as Biomarkers for Parkinson’s Disease: How Far from Clinical Translation?
by Alice Gualerzi, Silvia Picciolini, Marzia Bedoni, Franca Rosa Guerini, Mario Clerici and Cristina Agliardi
Int. J. Mol. Sci. 2024, 25(2), 1136; https://doi.org/10.3390/ijms25021136 - 17 Jan 2024
Viewed by 1171
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder affecting about 10 million people worldwide with a prevalence of about 2% in the over-80 population. The disease brings in also a huge annual economic burden, recently estimated by the Michael J Fox Foundation for Parkinson’s [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative disorder affecting about 10 million people worldwide with a prevalence of about 2% in the over-80 population. The disease brings in also a huge annual economic burden, recently estimated by the Michael J Fox Foundation for Parkinson’s Research to be USD 52 billion in the United States alone. Currently, no effective cure exists, but available PD medical treatments are based on symptomatic prescriptions that include drugs, surgical approaches and rehabilitation treatment. Due to the complex biology of a PD brain, the design of clinical trials and the personalization of treatment strategies require the identification of accessible and measurable biomarkers to monitor the events induced by treatment and disease progression and to predict patients’ responsiveness. In the present review, we strive to briefly summarize current knowledge about PD biomarkers, focusing on the role of extracellular vesicles as active or involuntary carriers of disease-associated proteins, with particular attention to those research works that envision possible clinical applications. Full article
(This article belongs to the Special Issue New Challenges of Parkinson’s Disease)
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