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Advances in Parkinson’s Disease Research
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Advances in Parkinson’s Disease Research

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 1736

Special Issue Editor

Dr. Valentino Racki

E-Mail Website
Guest Editor
1. Department of Neurology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
2. Clinic of Neurology, Clinical Hospital Center Rijeka, Rijeka, Croatia
Interests: movement disorders; Parkinson’s disease; deep brain stimulation; infusion therapies; atypical parkinsonism; neurodegeneration; gut–brain axis; neuroimmunology; biomarkers; precision medicine; microglia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Parkinson’s disease (PD) represents one of the fastest-growing neurodegenerative disorders worldwide, with profound clinical, social, and economic impacts. Despite significant advances in our understanding of its molecular mechanisms and therapeutic options, PD remains an incurable and heterogeneous disease, requiring integrative and multidisciplinary approaches. In recent years, rapid progress has been made in several areas, including genetics and molecular pathways of neurodegeneration, the role of neuroinflammation and the gut–brain axis, development of biomarkers for earlier and more precise diagnosis, and innovations in advanced therapies such as deep brain stimulation, infusion treatments, and novel pharmacological strategies. This Special Issue, titled “Advances in Parkinson’s Disease Research”, will highlight recent progress in basic, translational, and clinical research that can improve our understanding and management of PD. We welcome original research articles, reviews and perspectives covering topics such as disease pathophysiology, biomarker discovery, personalized medicine and new therapeutic approaches. By gathering contributions from diverse fields, this Special Issue will provide an updated and comprehensive overview of emerging directions in PD research and treatment.

Dr. Valentino Racki
Guest Editor

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.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 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
  • movement disorders
  • neurodegeneration
  • biomarkers
  • deep brain stimulation
  • infusion therapies
  • gut–brain axis
  • neuroinflammation
  • personalized medicine
  • atypical parkinsonism

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Published Papers (4 papers)

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Research

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21 pages, 335 KB  
Article
Pulmonary Function in Parkinson’s Disease: A Comparative Study of Spirometry and Impulse Oscillometry
by Alexandra-Cristiana Gache, Elena Danteș, Ariadna-Petronela Fildan, Andreea-Cristina Postu, Viorica Zamfir, Adina-Milena Man, Nicoleta-Larisa Șerban, Irene Rășanu and Any Axelerad
Biomedicines 2026, 14(5), 1176; https://doi.org/10.3390/biomedicines14051176 (registering DOI) - 21 May 2026
Abstract
Background/Objectives: Respiratory dysfunction in Parkinson’s disease (PD) is a clinically relevant but frequently underrecognized manifestation associated with functional impairment and increased risk of respiratory complications. This study compared spirometry and impulse oscillometry (IOS) in the assessment of respiratory function in PD, with particular [...] Read more.
Background/Objectives: Respiratory dysfunction in Parkinson’s disease (PD) is a clinically relevant but frequently underrecognized manifestation associated with functional impairment and increased risk of respiratory complications. This study compared spirometry and impulse oscillometry (IOS) in the assessment of respiratory function in PD, with particular focus on the detection of subtle or peripheral airway abnormalities. Methods: A prospective, single-center, cross-sectional study was conducted, including 108 participants (55 patients with PD and 53 control subjects). Pulmonary function was evaluated using standardized spirometry and IOS protocols. Group comparisons were performed using non-parametric tests, while multivariable regression analyses adjusted for potential confounding factors, including age, body mass index, smoking status, pollutant exposure, and cardiovascular comorbidities. Results: IOS identified a higher frequency of abnormal categorical findings compared with spirometry, including among subjects with normal spirometric values. Although dyspnea was more frequent in patients with PD in unadjusted analyses, multivariable regression demonstrated that PD was not an independent predictor of respiratory dysfunction. Pollutant exposure was significantly associated with abnormal IOS findings (p = 0.011). No significant differences were observed between PD and control groups regarding continuous spirometric or oscillometric parameters. Only a weak association between disease severity and FEV1 (%) was identified, whereas no significant correlations were observed for oscillometric parameters. Conclusions: IOS may provide complementary information regarding subtle or peripheral respiratory abnormalities in patients with PD. The findings suggest that respiratory alterations in this population are likely multifactorial and not independently determined by PD itself. Incorporating oscillometric assessment into respiratory evaluation may contribute to the identification of subtle respiratory mechanical alterations in patients with PD. Full article
(This article belongs to the Special Issue Advances in Parkinson’s Disease Research)
11 pages, 230 KB  
Article
Gothelf’s Haplotype of COMT in Parkinson’s Disease: A Case–Control Study
by Zdenko Červenák, Ján Somorčík, Žaneta Zajacová, Andrea Gažová, Igor Straka, Zuzana André, Michal Minár and Ján Kyselovič
Biomedicines 2026, 14(2), 262; https://doi.org/10.3390/biomedicines14020262 - 23 Jan 2026
Viewed by 691
Abstract
Background: Catechol-O-methyltransferase (COMT) catalyzes catecholamine O-methylation and contributes to dopamine turnover, potentially influencing levodopa requirements in Parkinson’s disease (PD). We evaluated whether the Gothelf COMT haplotype—and its constituent variants rs2075507, rs4680 (Val158Met), and rs165599—differ in frequency between PD cases and controls. We then [...] Read more.
Background: Catechol-O-methyltransferase (COMT) catalyzes catecholamine O-methylation and contributes to dopamine turnover, potentially influencing levodopa requirements in Parkinson’s disease (PD). We evaluated whether the Gothelf COMT haplotype—and its constituent variants rs2075507, rs4680 (Val158Met), and rs165599—differ in frequency between PD cases and controls. We then tested associations between these variants and clinical phenotypes, with a prespecified focus on levodopa equivalent daily dose (LEDD). Finally, we examined whether haplotype structure and allele-specific context (e.g., background-dependent effects) help explain observed genotype–phenotype relationships in the PD cohort. Aim: Analysis of the rs2075507, rs4680 and rs165599 at individual and haplotype level between control and diseased groups. Furthermore, analysis of association of individual SNPs or haplotype level with clinical outcomes. Subjects and methods: Fifty-five individuals with Parkinson’s disease (PD) and fifty-three neurologically healthy controls were enrolled at a single center. Genomic DNA was isolated from peripheral blood, and three COMT variants—rs2075507 (promoter), rs4680/Val158Met (coding), and rs165599 (3′UTR)—were genotyped by Sanger sequencing. Allele, genotype, and tri-marker haplotype frequencies were estimated, and case–control differences were evaluated. Within the PD cohort, associations with clinical outcomes—primarily levodopa equivalent daily dose (LEDD)—were analyzed using multivariable linear models. Statistical tests were two-sided, with multiplicity control as specified in the corresponding tables. Results: The rs2075507 polymorphism showed a robust additive association with LEDD; each A allele predicted higher dose (LEDD ≈ +1331 mg/day, p = 0.001) after adjusting for age and sex. The tri-haplotype test did not show significant association with LEDD. Nevertheless, rs2075507 SNP strongly marked downstream backgrounds: in AA carriers, rs4680–rs165599 haplotypes were enriched for Val (G) and rs165599-G; in GG carriers, for rs165599-A with mixed Val/Met; and GA was A-loaded at both loci. Exact tests confirmed that AA and GG differed in rs4680–rs165599 composition, whereas GA vs. GG was not significant. Conclusions: The promoter variation at rs2075507 may represent the genetic contributor to levodopa dose requirements when modeled with SNP–SNP interactions, with its effect is modified mostly by rs165599 polymorphism. Tri-haplotypes do not independently predict LEDD. The rs4680 (coding) and rs165599 (3′UTR) context appears to fine-tune rather than determine dosing needs, mainly via interaction with rs2075507 SNP. Full article
(This article belongs to the Special Issue Advances in Parkinson’s Disease Research)

Review

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25 pages, 460 KB  
Review
From Stress to Neurodegeneration: A New Look at the Pathogenesis of Parkinson’s Disease
by Rogneda B. Kazanskaya, Vassiliy Tsytsarev, Anna B. Volnova, Raul R. Gainetdinov and Alexander V. Lopachev
Biomedicines 2026, 14(5), 1130; https://doi.org/10.3390/biomedicines14051130 - 16 May 2026
Viewed by 179
Abstract
The relationship between stress and Parkinson’s disease is regarded as complex and multifaceted, although a direct causal link has not yet been conclusively proven. One prevailing hypothesis is based on the activation of the hypothalamic–pituitary–adrenal (HPA) axis and the consequent elevation of glucocorticoid [...] Read more.
The relationship between stress and Parkinson’s disease is regarded as complex and multifaceted, although a direct causal link has not yet been conclusively proven. One prevailing hypothesis is based on the activation of the hypothalamic–pituitary–adrenal (HPA) axis and the consequent elevation of glucocorticoid levels. Prolonged exposure to these hormones may exacerbate oxidative stress, thereby rendering the dopaminergic neurons within the brain’s subcortical structures more susceptible to degeneration. Furthermore, stress may intensify neuroinflammation through the activation of microglia—a mechanism that could constitute a significant factor in the pathogenesis of Parkinson’s disease. Another important concept concerns the direct interaction of stressors with the dopaminergic system. Physiological and psychological stress can alter dopaminergic transmission by affecting both the synthesis and release of dopamine, as well as the sensitivity of dopamine receptors. Severe or chronic stress may contribute to the disruption of dopaminergic mechanisms and accelerate the onset of clinical symptoms in predisposed individuals. Furthermore, many researchers draw attention to the role of stress-induced aggregation of α-synuclein—a key protein implicated in the pathogenesis of Parkinson’s disease. Clinical data suggest a highly probable link between post-traumatic stress disorder and an increased risk of developing Parkinson’s disease, although these findings remain inconclusive. It is possible that stress acts not as a primary cause, but rather as a modifying factor that interacts with genetic predisposition, accelerating or triggering neurodegenerative processes. The aim of our narrative review was to examine these concepts and discuss possible directions for future research into the interaction between stress and Parkinson’s disease. Full article
(This article belongs to the Special Issue Advances in Parkinson’s Disease Research)
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Other

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7 pages, 216 KB  
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Transcranial Sonography in the Examination of Atypical Parkinsonian Syndromes
by Piotr Alster, Bartosz Migda, Michał Kutyłowski, Michał Markiewicz and Natalia Madetko-Alster
Biomedicines 2026, 14(3), 530; https://doi.org/10.3390/biomedicines14030530 - 27 Feb 2026
Viewed by 453
Abstract
Transcranial sonography is one of the methods of examination used in atypical parkinsonian syndromes. The assessment is not indicated in the diagnostic criteria of entities in this group e.g., Progressive Supranuclear Palsy, Corticobasal Degeneration, Multiple System Atrophy and Dementia with Lewy Bodies. Atypical [...] Read more.
Transcranial sonography is one of the methods of examination used in atypical parkinsonian syndromes. The assessment is not indicated in the diagnostic criteria of entities in this group e.g., Progressive Supranuclear Palsy, Corticobasal Degeneration, Multiple System Atrophy and Dementia with Lewy Bodies. Atypical parkinsonisms are a group of diseases affected by diverse pathologies including alpha-synuclein or tau among others. Recently broader attention was brought to less common atypical parkinsonisms as Perry syndrome. Atypical parkinsonisms are related to poor response to levodopa treatment, rapid deterioration and unfavorable prognosis. Additionally, the entities often overlap in terms of clinical manifestation, especially in the early stages. Though atypical parkinsonisms are affected by the lack of possibility of obtaining definite in vivo diagnosis, growing interest is associated to supplementary evaluations including neuroimaging. Among these methods could be mentioned magnetic resonance imaging, positron emission tomography, single photon emission computed tomography and transcranial sonography. Transcranial sonography is associated with high accessibility and low cost. The goal of this paper is to highlight the strengths and weaknesses of transcranial sonography in the examination of atypical parkinsonisms. Full article
(This article belongs to the Special Issue Advances in Parkinson’s Disease Research)
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