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Keywords = dopaminergic loss

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16 pages, 4427 KiB  
Article
Garlic-Derived Allicin Attenuates Parkinson’s Disease via PKA/p-CREB/BDNF/DAT Pathway Activation and Apoptotic Inhibition
by Wanchen Zeng, Yingkai Wang, Yang Liu, Xiaomin Liu and Zhongquan Qi
Molecules 2025, 30(15), 3265; https://doi.org/10.3390/molecules30153265 - 4 Aug 2025
Abstract
Allicin (ALC), a naturally occurring organosulfur compound derived from garlic (Allium sativum), exhibits potential neuroprotective properties. Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by degeneration of dopaminergic neurons and motor dysfunction. This study utilized bioinformatics and network pharmacology methods [...] Read more.
Allicin (ALC), a naturally occurring organosulfur compound derived from garlic (Allium sativum), exhibits potential neuroprotective properties. Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by degeneration of dopaminergic neurons and motor dysfunction. This study utilized bioinformatics and network pharmacology methods to predict the anti-PD mechanism of ALC and established in vivo and in vitro PD models using 6-hydroxydopamine (6-OHDA) for experimental verification. Network pharmacological analysis indicates that apoptosis regulation and the PKA/p-CREB/BDNF signaling pathway are closely related to the anti-PD effect of ALC, and protein kinase A (PKA) and dopamine transporter (DAT) are key molecular targets. The experimental results show that ALC administration can alleviate the cytotoxicity of SH-SY5Y induced by 6-OHDA and simultaneously improve the motor dysfunction and dopaminergic neuron loss in PD mice. In addition, ALC can also activate the PKA/p-CREB/BDNF signaling pathway and increase the DAT level in brain tissue, regulate the expression of BAX and Bcl-2, and reduce neuronal apoptosis. These results indicate that ALC can exert anti-PD effects by up-regulating the PKA/p-CREB/BDNF/DAT signaling pathway and inhibiting neuronal apoptosis, providing theoretical support for the application of ALC in PD. Full article
(This article belongs to the Topic Natural Products and Drug Discovery—2nd Edition)
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21 pages, 2932 KiB  
Article
Stable Dopamine-Signaling mRNA Co-Expression in the Substantia Nigra Is Deregulated in Pathological Conditions, but Not in Dopamine Transporter Knockout Rats
by Anastasia N. Vaganova, Zoia S. Fesenko, Anna B. Volnova and Raul R. Gainetdinov
Biomolecules 2025, 15(8), 1117; https://doi.org/10.3390/biom15081117 - 3 Aug 2025
Viewed by 203
Abstract
Dopamine transporter (DAT) mutations are associated with neurological and psychiatric diseases, and DAT gene knockout in rats (DAT-KO) provides an opportunity to evaluate the DAT role in pathological conditions. We analyzed DAT expression and co-expression with other genes in the substantia nigra and [...] Read more.
Dopamine transporter (DAT) mutations are associated with neurological and psychiatric diseases, and DAT gene knockout in rats (DAT-KO) provides an opportunity to evaluate the DAT role in pathological conditions. We analyzed DAT expression and co-expression with other genes in the substantia nigra and striatum in public transcriptomic data represented in the GEO repository and then estimated the identified DAT co-expression pattern in DAT-KO rats by RT-PCR. In silico analysis confirmed DAT expression in the substantia nigra and absence of DAT mRNA in the striatum. Also, DAT is co-expressed with genes involved in dopamine signaling, but these associations are disrupted in dopamine neuron-damaging conditions. To estimate this co-expression pattern when DAT expression is lost, we evaluate it in the substantia nigra of DAT-KO rats. However, in DAT-KO rats the associations between genes involved in dopamine signaling were not disturbed compared to wild-type littermates, and tyrosine hydroxylase expression upregulation in the substantia nigra of these animals may be considered as compensation for the loss of dopamine reuptake. Further studies of expression regulation in dopamine neurons of DAT-KO rats may provide valuable information for compensatory mechanisms in substantia nigra dopaminergic neurons. Full article
(This article belongs to the Section Molecular Biology)
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13 pages, 1698 KiB  
Review
Systematic Review of Parkinsonism in Cerebrotendinous Xanthomatosis
by Jennifer Hanson and Penelope E. Bonnen
Neurol. Int. 2025, 17(8), 117; https://doi.org/10.3390/neurolint17080117 - 30 Jul 2025
Viewed by 214
Abstract
Background: Cerebrotendinous Xanthomatosis (CTX) is a rare, inherited metabolic disease caused by pathogenic variants in CYP27A1. The clinical presentation of this progressive disease includes cognitive deficits, ataxia, peripheral neuropathy, and pyramidal signs, as well as bilateral cataracts and tendon xanthomas. In some [...] Read more.
Background: Cerebrotendinous Xanthomatosis (CTX) is a rare, inherited metabolic disease caused by pathogenic variants in CYP27A1. The clinical presentation of this progressive disease includes cognitive deficits, ataxia, peripheral neuropathy, and pyramidal signs, as well as bilateral cataracts and tendon xanthomas. In some cases, CTX also includes parkinsonism. The goals of this study are to develop a data source that provides improved characterization and awareness of parkinsonism in CTX. Methods: We conducted a systematic review of the literature according to PRISMA guidelines to identify all published individuals diagnosed with CTX and parkinsonism. Clinical signs, imaging findings and treatment response to both chenodeoxycholic acid and dopaminergic medications were examined for 72 subjects. Results: The average age of onset of parkinsonism in these CTX patients was 42 years, illustrating the early onset nature of parkinsonism in CTX. Functional dopaminergic imaging revealed the loss of presynaptic dopaminergic neurons in the substantia nigra which points to neurodegeneration of the dopaminergic system as the underlying pathophysiology for parkinsonism in CTX. Brain MRI showed abnormalities in the basal ganglia in 38% of subjects. MRI also showed abnormalities in the cerebellum in 88% of subjects which is typical for CTX and can be utilized to distinguish subjects with CTX and parkinsonism from individuals with other forms of atypical parkinsonism. Dopaminergic medication mitigated parkinsonism signs in most individuals with CTX. Conclusion: CTX is a neurometabolic disease that can result in levodopa-responsive parkinsonism that should be included in the differential for atypical parkinsonism. Full article
(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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20 pages, 17080 KiB  
Article
Exercise Ameliorates Dopaminergic Neurodegeneration in Parkinson’s Disease Mice by Suppressing Microglia-Regulated Neuroinflammation Through Irisin/AMPK/Sirt1 Pathway
by Bin Wang, Nan Li, Yuanxin Wang, Xin Tian, Junjie Lin, Xin Zhang, Haocheng Xu, Yu Sun and Renqing Zhao
Biology 2025, 14(8), 955; https://doi.org/10.3390/biology14080955 - 29 Jul 2025
Viewed by 343
Abstract
Although exercise is known to exert anti-inflammatory effects in neurodegenerative diseases, its specific impact and underlying mechanisms in Parkinson’s disease (PD) remain poorly understood. This study explores the effects of exercise on microglia-mediated neuroinflammation and apoptosis in a PD model, focusing on the [...] Read more.
Although exercise is known to exert anti-inflammatory effects in neurodegenerative diseases, its specific impact and underlying mechanisms in Parkinson’s disease (PD) remain poorly understood. This study explores the effects of exercise on microglia-mediated neuroinflammation and apoptosis in a PD model, focusing on the role of irisin signaling in mediating these effects. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, we found that a 10-week treadmill exercise regimen significantly enhanced motor function, reduced dopaminergic neuron loss, attenuated neuronal apoptosis, and alleviated neuroinflammation. Exercise also shifted microglia from a pro-inflammatory to an anti-inflammatory phenotype. Notably, levels of irisin, phosphorylated AMP-activated protein kinase (p-AMPK), and sirtuin 1 (Sirt1), which were decreased in the PD brain, were significantly increased following exercise. These beneficial effects were abolished by blocking the irisin receptor with cyclic arginine–glycine–aspartic acid–tyrosine–lysine (cycloRGDyk). Our results indicate that exercise promotes neuroprotection in PD by modulating microglial activation and the AMPK/Sirt1 pathway through irisin signaling, offering new insights into exercise-based therapeutic approaches for PD. Full article
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29 pages, 23179 KiB  
Article
Oligodendrocyte-Specific STAT5B Overexpression Ameliorates Myelin Impairment in Experimental Models of Parkinson’s Disease
by Yibo Li, Zhaowen Su, Jitong Zhai, Qing Liu, Hongfang Wang, Jiaxin Hao, Xiaofeng Tian, Jiamin Gao, Dandan Geng and Lei Wang
Cells 2025, 14(15), 1145; https://doi.org/10.3390/cells14151145 - 25 Jul 2025
Viewed by 504
Abstract
Background: Parkinson’s disease (PD) involves progressive dopaminergic neuron degeneration and motor deficits. Oligodendrocyte dysfunction contributes to PD pathogenesis through impaired myelination. Methods: Single-nucleus RNA sequencing (snRNA-seq) of PD mice revealed compromised oligodendrocyte differentiation and STAT5B downregulation. Pseudotemporal trajectory analysis via Monocle2 demonstrated impaired [...] Read more.
Background: Parkinson’s disease (PD) involves progressive dopaminergic neuron degeneration and motor deficits. Oligodendrocyte dysfunction contributes to PD pathogenesis through impaired myelination. Methods: Single-nucleus RNA sequencing (snRNA-seq) of PD mice revealed compromised oligodendrocyte differentiation and STAT5B downregulation. Pseudotemporal trajectory analysis via Monocle2 demonstrated impaired oligodendrocyte maturation in PD oligodendrocytes, correlating with reduced myelin-related gene expression (Sox10, Plp1, Mbp, Mog, Mag, Mobp). DoRothEA-predicted regulon activity identified STAT5B as a key transcriptional regulator. Results: Oligodendrocyte-specific STAT5B activation improved myelin integrity, as validated by Luxol Fast Blue staining and transmission electron microscopy; attenuated dopaminergic neuron loss; and improved motor function. Mechanistically, STAT5B binds the MBP promoter to drive transcription, a finding confirmed by the luciferase assay, while the DNMT3A-mediated hypermethylation of the STAT5B promoter epigenetically silences its expression, as verified by MethylTarget sequencing and methylation-specific PCR. Conclusions: DNMT3A inhibited the expression of STAT5B by affecting its methylation, which reduced the transcription of MBP, caused oligodendrocyte myelin damage, and eventually led to dopamine neuron damage and motor dysfunction in an MPTP-induced mouse model. This DNMT3A-STAT5B-MBP axis underlies PD-associated myelin damage, connecting epigenetic dysregulation with oligodendrocyte dysfunction and subsequent PD pathogenesis. Full article
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25 pages, 1566 KiB  
Article
Combining QSAR and Molecular Docking for the Methodological Design of Novel Radiotracers Targeting Parkinson’s Disease
by Juan A. Castillo-Garit, Mar Soria-Merino, Karel Mena-Ulecia, Mónica Romero-Otero, Virginia Pérez-Doñate, Francisco Torrens and Facundo Pérez-Giménez
Appl. Sci. 2025, 15(15), 8134; https://doi.org/10.3390/app15158134 - 22 Jul 2025
Viewed by 269
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder marked by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. The dopamine active transporter (DAT), a key protein involved in dopamine reuptake, serves as a selective biomarker for dopaminergic terminals in the striatum. DAT [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative disorder marked by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. The dopamine active transporter (DAT), a key protein involved in dopamine reuptake, serves as a selective biomarker for dopaminergic terminals in the striatum. DAT binding has been extensively studied using in vivo imaging techniques such as Single-Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET). To support the design of new radiotracers targeting DAT, we employ Quantitative Structure–Activity Relationship (QSAR) analysis on a structurally diverse dataset composed of 57 compounds with known affinity constants for DAT. The best-performing QSAR model includes four molecular descriptors and demonstrates robust statistical performance: R2 = 0.7554, Q2LOO = 0.6800, and external R2 = 0.7090. These values indicate strong predictive capability and model stability. The predicted compounds are evaluated using a docking methodology to check the correct coupling and interactions with the DAT. The proposed approach—combining QSAR modeling and docking—offers a valuable strategy for screening and optimizing potential PET/SPECT radiotracers, ultimately aiding in the neuroimaging and early diagnosis of Parkinson’s disease. Full article
(This article belongs to the Special Issue Application of Artificial Intelligence in Biomedical Informatics)
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27 pages, 977 KiB  
Review
Branched-Chain Amino Acids in Parkinson’s Disease: Molecular Mechanisms and Therapeutic Potential
by Hui-Yu Huang, Shu-Ping Tsao and Tu-Hsueh Yeh
Int. J. Mol. Sci. 2025, 26(14), 6992; https://doi.org/10.3390/ijms26146992 - 21 Jul 2025
Viewed by 366
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra, resulting in motor symptoms such as bradykinesia, tremor, rigidity, and postural instability, as well as a wide variety of non-motor manifestations. Branched-chain amino [...] Read more.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra, resulting in motor symptoms such as bradykinesia, tremor, rigidity, and postural instability, as well as a wide variety of non-motor manifestations. Branched-chain amino acids (BCAAs)—leucine, isoleucine, and valine—are essential nutrients involved in neurotransmitter synthesis, energy metabolism, and cellular signaling. Emerging evidence suggests that BCAA metabolism is intricately linked to the pathophysiology of PD. Dysregulation of BCAA levels has been associated with energy metabolism, mitochondrial dysfunction, oxidative stress, neuroinflammation, and altered neurotransmission. Furthermore, the branched-chain ketoacid dehydrogenase kinase (BCKDK), a key regulator of BCAA catabolism, has been implicated in PD through its role in modulating neuronal energetics and redox homeostasis. In this review, we synthesize current molecular, genetic, microbiome, and clinical evidence on BCAA dysregulation in PD to provide an integrative perspective on the BCAA–PD axis and highlight directions for future translational research. We explored the dualistic role of BCAAs as both potential neuroprotective agents and metabolic stressors, and critically examined the therapeutic prospects and limitations of BCAA supplementation and BCKDK targeting. Full article
(This article belongs to the Special Issue Molecular Research in Parkinson's Disease)
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14 pages, 4042 KiB  
Article
Conditional Deletion of Translin/Trax in Dopaminergic Neurons Reveals No Impact on Psychostimulant Behaviors or Adiposity
by Yunlong Liu, Renkun Wu, Gaiyuan Geng, Helian Yang, Chunmiao Wang, Mengtian Ren and Xiuping Fu
Biomolecules 2025, 15(7), 1040; https://doi.org/10.3390/biom15071040 - 17 Jul 2025
Viewed by 329
Abstract
Despite the abundant expression of the microRNA-degrading Translin (TN)/Trax (TX) complex in midbrain dopaminergic (DA) neurons and its implication in neuropsychiatric disorders, its cell-autonomous roles in metabolic and behavioral responses remain unclear. To address this, we generated DA neuron-specific conditional knockout (cKO) mice [...] Read more.
Despite the abundant expression of the microRNA-degrading Translin (TN)/Trax (TX) complex in midbrain dopaminergic (DA) neurons and its implication in neuropsychiatric disorders, its cell-autonomous roles in metabolic and behavioral responses remain unclear. To address this, we generated DA neuron-specific conditional knockout (cKO) mice for Tsn (TN) or Tsnax (TX) using DAT-Cre. Immunostaining confirmed efficient TX loss in Tsnax cKO DA neurons without affecting TN, while Tsn deletion abolished TX expression, revealing asymmetric protein dependency. Body composition analysis showed no alterations in adiposity in either cKO model. Locomotor responses to acute or repeated administration of cocaine (20 mg/kg) or amphetamine (2.5 mg/kg) were unchanged in Tsn or Tsnax cKO mice. Furthermore, amphetamine-induced conditioned place preference (1 mg/kg) was unaffected. These results demonstrate that the TN/TX complex within DA neurons is dispensable for regulating adiposity, psychostimulant-induced locomotion (both acute and sensitized), or amphetamine reward-related behavior, suggesting its critical functions may lie outside these specific domains. Full article
(This article belongs to the Section Molecular Genetics)
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38 pages, 1540 KiB  
Review
Understanding the Pre-Clinical Stages of Parkinson’s Disease: Where Are We in Clinical and Research Settings?
by Camilla Dalla Verde, Sri Jayanti, Korri El Khobar, John A. Stanford, Claudio Tiribelli and Silvia Gazzin
Int. J. Mol. Sci. 2025, 26(14), 6881; https://doi.org/10.3390/ijms26146881 - 17 Jul 2025
Viewed by 1258
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the world. PD is characterized by motor and non-motor symptoms, but the diagnosis primarily relies on the clinical assessment of postural and movement abnormalities, supported by imaging and genetic testing. It is [...] Read more.
Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the world. PD is characterized by motor and non-motor symptoms, but the diagnosis primarily relies on the clinical assessment of postural and movement abnormalities, supported by imaging and genetic testing. It is widely accepted that the disease process begins decades before the onset of overt symptoms. Emerging evidence suggests that neuroinflammation plays a central role in the pathogenesis of PD, particularly during the pre-clinical phase. Activated microglia, increased levels of pro-inflammatory cytokines, and persistent oxidative stress have all been associated with the gradual loss of dopaminergic neurons. Although earlier detection and diagnosis remain elusive, achieving these goals is crucial for advancing prevention and disease-modifying strategies. Clinical studies are ongoing. To fill the gap, research models that recapitulate the chronic disease progression of PD are crucial to test preventive and disease-modifying strategies. This review briefly summarizes clinical knowledge on PD as a starting point for improving research models. Furthermore, we will critically evaluate how the existing models have been utilized and highlight opportunities to overcome their limitations and enhance the translational relevance to clinical application. Full article
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21 pages, 1875 KiB  
Review
Translating Exosomal microRNAs from Bench to Bedside in Parkinson’s Disease
by Oscar Arias-Carrión, María Paulina Reyes-Mata, Joaquín Zúñiga and Daniel Ortuño-Sahagún
Brain Sci. 2025, 15(7), 756; https://doi.org/10.3390/brainsci15070756 - 16 Jul 2025
Viewed by 407
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by dopaminergic neuronal loss, α-synuclein aggregation, and chronic neuroinflammation. Recent evidence suggests that exosomal microRNAs (miRNAs)—small, non-coding RNAs encapsulated in extracellular vesicles—are key regulators of PD pathophysiology and promising candidates for biomarker development and [...] Read more.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by dopaminergic neuronal loss, α-synuclein aggregation, and chronic neuroinflammation. Recent evidence suggests that exosomal microRNAs (miRNAs)—small, non-coding RNAs encapsulated in extracellular vesicles—are key regulators of PD pathophysiology and promising candidates for biomarker development and therapeutic intervention. Exosomes facilitate intercellular communication, cross the blood–brain barrier, and protect miRNAs from degradation, rendering them suitable for non-invasive diagnostics and targeted delivery. Specific exosomal miRNAs modulate neuroinflammatory cascades, oxidative stress, and synaptic dysfunction, and their altered expression in cerebrospinal fluid and plasma correlates with disease onset, severity, and progression. Despite their translational promise, challenges persist, including methodological variability in exosome isolation, miRNA profiling, and delivery strategies. This review integrates findings from preclinical models, patient-derived samples, and systems biology to delineate the functional impact of exosomal miRNAs in PD. We propose mechanistic hypotheses linking miRNA dysregulation to molecular pathogenesis and present an interactome model highlighting therapeutic nodes. Advancing exosomal miRNA research may transform the clinical management of PD by enabling earlier diagnosis, molecular stratification, and the development of disease-modifying therapies. Full article
(This article belongs to the Special Issue Molecular Insights in Neurodegeneration)
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6 pages, 4382 KiB  
Interesting Images
Whole-Brain Confocal Imaging Provides an Accurate Global View of the Nigral Dopamine System
by Fu-Ming Zhou
Diagnostics 2025, 15(11), 1436; https://doi.org/10.3390/diagnostics15111436 - 5 Jun 2025
Viewed by 625
Abstract
Clinicopathological studies and the effectiveness of dopaminergic replacement therapy establish that dopamine loss is the key pathology causing motor symptoms in Parkinson’s disease. The dopamine neurons that are impaired in Parkinson’s disease reside in the substantia nigra and ventral tegmental area in the [...] Read more.
Clinicopathological studies and the effectiveness of dopaminergic replacement therapy establish that dopamine loss is the key pathology causing motor symptoms in Parkinson’s disease. The dopamine neurons that are impaired in Parkinson’s disease reside in the substantia nigra and ventral tegmental area in the midbrain. These neurons project into the striatum, where dopamine axons bifurcate repeatedly and form dense axon networks (the striatum is separated into the caudate nucleus and putamen by the internal capsule). Midbrain dopamine neurons also innervate many other areas of the brain, including the cerebral cortex. Therefore, there are preclinical and clinical studies investigating extrastriatal dopamine mechanisms in motor control and Parkinson’s disease pathophysiology and treatment. While extrastriatal dopamine can contribute, this contribution needs to be compared with the contribution of the striatal dopamine system. An isolated view of the extrastriatal dopamine system is like examining only the ear of an elephant and may lead to distorted assessments for preclinical and clinical research and diagnostic work. Thus, photographs of the whole brain dopamine system are important. For these reasons, we photographed the dopamine systems in whole mouse brain sagittal sections, showing clearly that, under identical imaging conditions, dopamine innervation is highly concentrated and intense in the striatum but sparse and weak in the cerebral cortex. Full article
(This article belongs to the Section Biomedical Optics)
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24 pages, 574 KiB  
Systematic Review
Tissue Stem Cell-Based Therapies in Parkinson’s Disease: A Scoping Review of Therapeutic Mechanisms and Translational Outcomes
by Emily Cueva, Andrea Wiesheu, Zaira Sordo, Jailene González, Sabine Falconi, Jose A. Rodas and Jose E. Leon-Rojas
Cells 2025, 14(11), 822; https://doi.org/10.3390/cells14110822 - 1 Jun 2025
Viewed by 1054
Abstract
(1) Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by dopaminergic neuronal loss. Tissue stem cell-based therapies have emerged as promising candidates for disease modification and symptomatic relief. This scoping review aims to systematically synthesise the literature on tissue stem cell [...] Read more.
(1) Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by dopaminergic neuronal loss. Tissue stem cell-based therapies have emerged as promising candidates for disease modification and symptomatic relief. This scoping review aims to systematically synthesise the literature on tissue stem cell therapies for PD across cellular, animal, and human studies, with a focus on transplantation strategies, mechanisms of action, and therapeutic outcomes. (2) Methods: We identified 1017 records by querying PubMed, Scopus, Cochrane, and the Virtual Health Library. After screening and applying eligibility criteria, 33 experimental studies were included. Data were extracted on study design, tissue stem cell source, type of subject, and therapeutic effects. (3) Results: Most studies (n = 25) involved animal models, with a minority (n = 8) focusing on human applications. Tissue stem cell therapies showed potential to promote dopaminergic differentiation, reduce inflammation and apoptosis, and improve behavioural and motor outcomes. Autologous transplants yielded a higher safety and efficacy compared to allogeneic ones. The beneficial mechanisms of tissue stem cells included neurotrophic support, mitochondrial protection, modulation of the gut–brain axis, and α-synuclein clearance. (4) Conclusions: Tissue stem cell therapies represent a promising approach for PD. However, standardised protocols and long-term safety assessments are essential to optimise their translational potential. Full article
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20 pages, 1638 KiB  
Article
Prediction of 123I-FP-CIT SPECT Results from First Acquired Projections Using Artificial Intelligence
by Wadi’ Othmani, Arthur Coste, Dimitri Papathanassiou and David Morland
Diagnostics 2025, 15(11), 1407; https://doi.org/10.3390/diagnostics15111407 - 31 May 2025
Viewed by 551
Abstract
Background/Objectives: 123I-FP-CIT dopamine transporter imaging is commonly used for the diagnosis of Parkinsonian syndromes in patients whose clinical presentation is atypical. Prolonged immobility, which can be difficult to maintain in this population, is required to perform SPECT acquisition. In this study we aimed [...] Read more.
Background/Objectives: 123I-FP-CIT dopamine transporter imaging is commonly used for the diagnosis of Parkinsonian syndromes in patients whose clinical presentation is atypical. Prolonged immobility, which can be difficult to maintain in this population, is required to perform SPECT acquisition. In this study we aimed to develop a Convolutional Neural Network (CNN) able to predict the outcome of the full examination based on the first acquired projection, and reliably detect normal patients. Methods: All 123I-FP-CIT SPECT performed in our center between June 2017 and February 2024 were included and split between a training and a validation set (70%/30%). An additional 100 SPECT were used as an independent test set. Examinations were labeled by two independent physicians. A VGG16-like CNN model was trained to assess the probability of examination abnormality from the first acquired projection (anterior and posterior view at 0°), taking age into consideration. A threshold maximizing sensitivity while maintaining good diagnostic accuracy was then determined. The model was validated in the independent testing set. Saliency maps were generated to visualize the most impactful areas in the classification. Results: A total of 982 123I-FP-CIT SPECT were retrieved and labelled (training set: 618; validation set: 264; independent testing set: 100). The trained model achieved a sensibility of 98.0% and a negative predictive value of 96.3% (one false negative) while maintaining an accuracy of 75.0%. The saliency maps confirmed that the regions with the greatest impact on the final classification corresponded to clinically relevant areas (basal ganglia and background noise). Conclusions: Our results suggest that this trained CNN could be used to exclude presynaptic dopaminergic loss with high reliability from the first acquired projection. It could be particularly useful in patients with compliance issues. Confirmation with images from other centers will be necessary. Full article
(This article belongs to the Special Issue Application of Neural Networks in Medical Diagnosis)
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36 pages, 1705 KiB  
Review
Caloric Restriction Mimetics as Priming Agents of Mesenchymal Stem Cells Secretome to Enhance Regenerative Responses to Parkinson’s Disease
by Bárbara Carneiro-Pereira, Filipa Ferreira-Antunes, Jonas Campos, António J. Salgado and Belém Sampaio-Marques
Molecules 2025, 30(11), 2260; https://doi.org/10.3390/molecules30112260 - 22 May 2025
Viewed by 932
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder primarily defined by the deterioration of motor function and characterized by the loss of dopaminergic neurons in the nigrostriatal system. Although it is the second most prevalent disorder of the central nervous system, current treatments primarily [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative disorder primarily defined by the deterioration of motor function and characterized by the loss of dopaminergic neurons in the nigrostriatal system. Although it is the second most prevalent disorder of the central nervous system, current treatments primarily focus on symptom management and modestly slowing disease progression, ultimately failing to preserve the long-term quality of life of a substantial proportion of affected individuals. Innovative therapies that can restore neuronal function have emerged, such as the use of the secretome of Mesenchymal Stem Cells (MSCs) due to their rich composition of bioactive molecules. This therapy exhibits robust paracrine activity that drives most of the self-renewal capacity, differentiation potential, and immune regulation of MSCs without presenting compatibility issues often associated with stem cell-based therapies. While conceptually appealing, the clinical application of this approach is still limited by the availability and proliferation capacity of MSCs, as it impacts not only secretome production but also its quality. Various protocols have been developed to enhance secretome action by adding various compounds to cell culture media, given the high environmental plasticity of MSCs. Some of the compounds already used are Caloric Restriction Mimetics (CRMs), molecules that mimic Caloric Restriction (CR) conditions, which have been demonstrated to extend lifespan and reduce age-related diseases in various organisms. While not sufficient to cure neurodegenerative disorders, these compounds may potentiate secretome efficiency by enhancing autophagy pathways and relieving oxidative stress burden from MSCs. Therefore, in this article, we aim to explore the effects of CRMs priming on MSCs and how it may help bridge existing gaps in regenerative therapies for PD. Full article
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15 pages, 678 KiB  
Article
Retinal Thickness in Patients with Parkinson’s Disease and Dopa Responsive Dystonia—Is There Any Difference?
by Marko Svetel, Gorica Marić, Marija Božić, Una Lazić, Andona Milovanović, Jana Jakšić, Igor Petrović, Ana Dimitrijević, Milica Knežević and Tatjana Pekmezović
Biomedicines 2025, 13(5), 1227; https://doi.org/10.3390/biomedicines13051227 - 19 May 2025
Viewed by 482
Abstract
Background/Objectives: Certain aspects of retinal thickness assessed by optical coherence tomography (OCT) in patients with Parkinson’s disease (PD) require additional clarification. It is supposed that attributing reduced retinal thickness in PD to dopaminergic loss may not be acceptable as it also happens [...] Read more.
Background/Objectives: Certain aspects of retinal thickness assessed by optical coherence tomography (OCT) in patients with Parkinson’s disease (PD) require additional clarification. It is supposed that attributing reduced retinal thickness in PD to dopaminergic loss may not be acceptable as it also happens in diseases where dopaminergic loss does not occur. The objective of our study is to compare the ganglion cell/inner plexiform layer (GCIPL), peripapillary retinal nerve fiber layer (pRNFL), and macular thickness of PD and dopa responsive dystonia (DRD) patients with healthy controls (HC), to investigate whether DRD patients, as a distinctive model of genetically induced dopamine deficiency, have reduced retinal thickness in comparison with PD, and to analyze correlation between retinal thickness and various PD clinical parameters. Methods: We analyzed 86 patients with PD, 10 patients with DRD, and 96 age- and sex-matched HC. Results: GCIPL, pRNFL, and central macula thickness (CMT) are statistically significantly thinner in PD patients compared to HC (p < 0.001, all). GCIPL and CMT are also statistically significantly thinner in DRD patients compared to HC (p = 0.012, p = 0.001, respectively). GCIPL thickness correlates positively with the daily dose of levodopa (r = 0.244, p < 0.01). The thickness of GCIPL and pRNFL correlate negatively with current age (r = −0.219; p < 0.01 and r = −0.358; p < 0.05, respectively). All retinal parameters are statistically significantly thinner in females than in males (p < 0.05). Conclusions: Patients with PD and DRD did not differ in GCIPL and pRNFL thickness when compared to one another. These results, supported by positive correlation of levodopa dose and GCIPL thickness in PD patients, emphasize the importance of dopamine in maintaining retinal thickness. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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