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Brain Sciences
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New Approaches in the Exploration of Parkinson’s Disease: 2nd Edition
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New Approaches in the Exploration of Parkinson’s Disease: 2nd Edition

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neurodegenerative Diseases".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 2246

Special Issue Editors

Dr. Carla Masala

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Guest Editor
Department of Biomedical Sciences, University of Cagliari, SP 8 Cittadella Universitaria, 09042 Monserrato, Italy
Interests: neurophysiology; chemoreception; neurodegenerative disease; mild cognitive impairment; neuroscience
Dr. Paolo Solla

E-Mail Website
Guest Editor
Department of Neurology, University of Sassari, Viale S. Pietro 10, 07100 Sassari, Italy
Interests: neurological disorders; Parkinson’s disease; Parkinsonism and related disorders
Special Issues, Collections and Topics in MDPI journals
Dr. Francesco Loy

E-Mail Website
Guest Editor
Department of Biomedical Sciences, University of Cagliari, SP 8 Cittadella Universitaria, 09042 Monserrato, Italy
Interests: electron microscopy; scanning electron microscopy; neuroanatomy
Special Issues, Collections and Topics in MDPI journals
Dr. Tommaso Ercoli

E-Mail Website
Guest Editor
Department of Neurology, University of Sassari, Viale S. Pietro 10, 07100 Sassari, Italy
Interests: movement disorders; neurology; Parkinsonism and related disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Parkinson’s disease (PD) is a chronic, complex progressive neurodegenerative disease defined by loss of dopaminergic neurons in the substantia nigra pars compacta situated in the midbrain and associated with Lewy bodies, which are cytoplasmic inclusions of alpha-synuclein aggregates. Clinical diagnosis of PD is based primarily on motor symptoms, such as a slow progressive asymmetric resting tremor, rigidity, and bradykinesia. Although non-motor symptoms, which include olfactory deficits, constipation, autonomic dysfunction, depression, and REM sleep behavior disorder, usually precede the presence of motor deficits.

Different factors may influence PD risk such as mitochondrial dysfunction, impaired autophagy, oxidative stress, protein aggregation, neuroinflammation, environmental and genetic status.

The aim of this Special Issue is to better characterize the PD, covering aspects related to the motor and non-motor symptoms which negatively affect health-related quality of life. For this purpose, we invite colleagues to share their recent research on this topic. Original research articles, review articles as well as short communications, and case reports are invited.

Dr. Carla Masala
Dr. Paolo Solla
Dr. Francesco Loy
Dr. Tommaso Ercoli
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 250 words) can be sent to the Editorial Office for assessment.

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. Brain Sciences 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 2200 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

  • Parkinson’s disease
  • neurodegenerative disorders
  • nonmotor symptoms
  • quality of life
  • cognition
  • olfactory deficits

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Published Papers (3 papers)

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Research

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11 pages, 1492 KB  
Article
Color Vision Deficits and Binocular Vision Dysfunction in Parkinson’s Disease
by Julia Mleczek, Anim Forjindam, Aasef Shaikh and Fatema Ghasia
Brain Sci. 2026, 16(2), 213; https://doi.org/10.3390/brainsci16020213 - 11 Feb 2026
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Abstract
Background/Objectives: Visual dysfunction is a common non-motor symptom in Parkinson’s Disease (PD), as evidenced by deficits in color vision (CV) and binocular vision (BV). Computerized CV tests, such as the Cambridge Color Test (CCT), are underutilized in this patient population despite the known [...] Read more.
Background/Objectives: Visual dysfunction is a common non-motor symptom in Parkinson’s Disease (PD), as evidenced by deficits in color vision (CV) and binocular vision (BV). Computerized CV tests, such as the Cambridge Color Test (CCT), are underutilized in this patient population despite the known limitations of common CV tests. Methods: In total, 19 PD and 12 control participants underwent a comprehensive eye exam, including ocular motility testing and the CCT, utilizing thresholds obtained along 12 contrast vectors to fit a discrimination ellipse. Findings were compared across groups, and the association with disease severity was analyzed. Results: PD participants showed increases in ellipse area (p = 0.012) and short-axis length (p = 0.009). PD participants demonstrated convergence insufficiency type exotropia (p < 0.001) and impaired stereopsis (p = 0.006). No significant correlation with UPDRS scores was seen for either BV or CV. Conclusions: PD participants exhibited binocular vision dysfunction with selective changes in color vision. CV changes are more variable in PD, likely due to mixed parvocellular and cortical dysfunction. Convergence insufficiency type exotropia is more common in PD, likely due to combined cortical and subcortical neurodegeneration. Both BV and CV changes occur independently of motor severity, emphasizing the need for routine visual testing regardless of symptom progression. Full article
(This article belongs to the Special Issue New Approaches in the Exploration of Parkinson’s Disease: 2nd Edition)
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Review

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23 pages, 1599 KB  
Review
Computational Modeling of Parkinson’s Disease Across Scales: From Mechanisms to Biomarkers, Drug Discovery, and Personalized Therapies
by Sandeep Sathyanandan Nair, Aratrik Guha, Srinivasa Chakravarthy and Aasef G. Shaikh
Brain Sci. 2026, 16(2), 175; https://doi.org/10.3390/brainsci16020175 - 31 Jan 2026
Viewed by 1075
Abstract
Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder characterized by complex interactions across molecular, cellular, circuit, and behavioral scales. While experimental and clinical studies have provided critical insights into PD pathology, integrating these heterogeneous data into coherent mechanistic frameworks and translational strategies remains [...] Read more.
Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder characterized by complex interactions across molecular, cellular, circuit, and behavioral scales. While experimental and clinical studies have provided critical insights into PD pathology, integrating these heterogeneous data into coherent mechanistic frameworks and translational strategies remains a major challenge. Computational modeling offers a powerful approach to bridge these scales, enabling the systematic investigation of disease mechanisms, candidate biomarkers, and therapeutic strategies. In this review, we survey state-of-the-art computational approaches applied to PD, spanning molecular dynamics and biophysical models, cellular- and circuit-level network models, systems and abstract-level simulations of basal ganglia function, and whole-brain and data-driven models linked to clinical phenotypes. We highlight how multiscale and hybrid modeling strategies connect α-synuclein pathology, mitochondrial dysfunction, oxidative stress, and dopaminergic degeneration to alterations in neural dynamics and motor and non-motor symptoms. We further discuss the role of computational models in biomarker discovery, including imaging, electrophysiological, and digital biomarkers. In particular, eye-movement-based measures are highlighted as quantitative, reproducible behavioral signals that provide principled constraints for individualized computational modeling. We also review the emerging impact of computational approaches on drug discovery, target prioritization, and in silico clinical trials. Finally, we examine future directions toward personalized and precision medicine in PD, emphasizing digital twin frameworks, longitudinal validation, and the integration of patient-specific data with mechanistic and data-driven models. Together, these advances underscore the growing role of computational modeling as an integrative and hypothesis-generating framework, with the long-term goal of supporting data-constrained predictive approaches for biomarker development and translational applications. Full article
(This article belongs to the Special Issue New Approaches in the Exploration of Parkinson’s Disease: 2nd Edition)
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Other

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8 pages, 336 KB  
Case Report
Opicapone as Add-On Therapy to Continuous Subcutaneous Foslevodopa/Foscarbidopa Infusion: Clinical Improvement and Wearable Sensor-Based Gait Analysis
by Paolo Solla, Carla Masala, Gianluca Martinez, Raffaele Galiero, Valentina Floris, Elisa Ogana, Valentina Canu, Francesco Loy and Tommaso Ercoli
Brain Sci. 2026, 16(5), 545; https://doi.org/10.3390/brainsci16050545 - 21 May 2026
Viewed by 129
Abstract
Background/Objectives: Continuous subcutaneous foslevodopa/foscarbidopa infusion (CSFLI) improves motor fluctuations in advanced Parkinson’s disease (PD), but some patients continue to experience residual motor and non-motor fluctuations despite optimized infusion parameters. We describe two patients receiving CSFLI in whom the addition or reintroduction of opicapone [...] Read more.
Background/Objectives: Continuous subcutaneous foslevodopa/foscarbidopa infusion (CSFLI) improves motor fluctuations in advanced Parkinson’s disease (PD), but some patients continue to experience residual motor and non-motor fluctuations despite optimized infusion parameters. We describe two patients receiving CSFLI in whom the addition or reintroduction of opicapone was associated with improvement in persistent fluctuations. In one patient, clinical findings were further explored using wearable sensor monitoring. Methods: Two patients with advanced PD treated with CSFLI and residual fluctuations received add-on opicapone. Clinical evaluation included neurological examination, assessment of motor fluctuations, and documentation of antiparkinsonian therapy before and after opicapone introduction. In one patient, motor performance was additionally evaluated with wearable sensor monitoring during the Timed Up and Go test and the 6-minute walk test before (T0) and three months after opicapone introduction (T1). Results: In both cases, opicapone 50 mg once daily was associated with rapid improvement in residual motor and non-motor fluctuations during CSFLI therapy. In the first patient, freezing episodes and unpredictable akinesia resolved. In the second patient, the reintroduction of opicapone improved morning slowness, axial symptoms, and dorsal pain. Wearable sensor analysis showed increased walking distance during the 6-minute walk test, higher walking speed, reduced Timed Up and Go duration, increased step length, and reduced step length variability. Conclusions: These preliminary observations suggest that opicapone may deserve further investigation as a potential adjunctive strategy in selected patients receiving CSFLI who continue to experience residual fluctuations despite optimized infusion therapy. Wearable sensor monitoring may provide objective support for treatment assessment in this setting. Full article
(This article belongs to the Special Issue New Approaches in the Exploration of Parkinson’s Disease: 2nd Edition)
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