Advances in Biomedical Research and Clinical Studies of Parkinson’s Disease and Atypical Parkinsonian Disorders

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

Deadline for manuscript submissions: 19 June 2026 | Viewed by 881

Special Issue Editors


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Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Interests: Parkinson’s disease; venous thrombosis; education (active learning and STEMM)
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Guest Editor
General Hospital “San Giuseppe” of Empoli, Florence, Viale Boccaccio, 50053 Empoli (FI), Italy
Interests: Parkinsonian disorders

Special Issue Information

Dear Colleagues,

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder in the older adult population. PD typically begins because of the loss of dopamine-producing neurons in the brain's substantia nigra pars compacta region. Lewy bodies, which are denatured aggregates of the protein a-synuclein, are found in these neuronal cells, the formation of which promotes dopaminergic neuronal cell dysfunction and death. PD typically presents as a movement disorder (symptoms including rigidity, slowness of movement, postural instability, and resting tremor). However, there are numerous comorbid non-motor symptoms in PD, including depression and psychosis, constipation, urinary disruption, and sleep disorders.

Parkinsonian syndromes (so-called “atypical parkinsonian disorders”) have been recognized as pathologically distinct, neurodegenerative conditions that mimic several of the symptoms of PD. The atypical parkinsonian syndromes are synucleinopathies and tauopathies, i.e., disorders characterized by the abnormal deposition of the proteins a-synuclein and tau, respectively. The site of deposition is correlated with the clinical features. Importantly, patients with these alternate conditions find their disease progression to carry greater and earlier morbidity and altered risks of mortality as compared to idiopathic PD. The atypical parkinsonian disorders include multiple system atrophy parkinsonian variant (MSA-P), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), dementia with Lewy Bodies (DLBs), and frontotemporal dementia (FTD).

This Topic on Parkinson’s disease and atypical parkinsonian disorders will provide an update of this complex neurodegenerative field, and it will offer the basis for future work in understanding these disorders. Manuscripts that include any aspect related to basic science models and complex systems (in vitro and in vivo), pathogenesis and the process(es) leading to disease (from prodrome to active disease), new genetic markers, new pharmaceutical drugs and targets, complementary and alternative medicine approaches, exercise/physical activity used as treatment and medicine, drug repurposing, clinical reports and studies, and reviews (systematic, meta-analysis, and narrative) will be considered appropriate for this Topic.

Dr. Frank C. Church
Dr. Stefania Brotini
Guest Editors

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Keywords

  • neurodegenerative diseases
  • Parkinson’s disease (PD)
  • atypical parkinsonian disorders (APDs)
  • Alzheimer’s disease (AD)
  • frontotemporal dementia (FTD)
  • Dementia with Lewy Body (DLB)
  • Multiple System Atrophy Parkinsonian Variant (MSA-P)
  • Progressive Supranuclear Palsy (PSP)
  • Corticobasal Degeneration (CBD)
  • biomarkers of PD and APD
  • pathophysiology of neurodegeneration in PD and APD
  • α-synuclein, beta-amyloid, and tau
  • role of exercise in therapy for neurodegenerative disorders (PD and APD)
  • recent discoveries in the genetics and therapies of neurodegenerative dementias in PD and APD
  • brain plasticity
  • Complementary &Alternative Medicine (CAM) approaches in PD and APD
  • research aimed to understand the role of neuroinflammation in PD and APD
  • advances in the role of a dysfunctional immune system in the etiology of PD and APD
  • mitochondria and cellular energy problems in PD and APD.

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Published Papers (1 paper)

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Research

14 pages, 691 KB  
Article
Epigenetic Signatures in an Italian Cohort of Parkinson’s Disease Patients from Sicily
by Maria Grazia Salluzzo, Francesca Ferraresi, Luca Marcolungo, Chiara Pirazzini, Katarzyna Malgorzata Kwiatkowska, Daniele Dall’Olio, Gastone Castellani, Claudia Sala, Elisa Zago, Davide Gentilini, Francesca A. Schillaci, Michele Salemi, Giuseppe Lanza, Raffaele Ferri and Paolo Garagnani
Brain Sci. 2026, 16(1), 31; https://doi.org/10.3390/brainsci16010031 - 25 Dec 2025
Viewed by 374
Abstract
Background/Objectives: Parkinson’s disease (PD) is an adult-onset neurodegenerative disorder whose pathogenesis is still not completely understood. Several lines of evidence suggest that alterations in epigenetic architecture may contribute to the development of this condition. Here, we present a pilot DNA methylation study [...] Read more.
Background/Objectives: Parkinson’s disease (PD) is an adult-onset neurodegenerative disorder whose pathogenesis is still not completely understood. Several lines of evidence suggest that alterations in epigenetic architecture may contribute to the development of this condition. Here, we present a pilot DNA methylation study from peripheral blood in a cohort of Sicilian PD patients and matched controls. Peripheral tissue analysis has previously been shown to reflect molecular and functional profiles relevant to neurological diseases, supporting their validity as a proxy for studying brain-related epigenetic mechanisms. Methods: We analyzed 20 PD patients and 20 healthy controls (19 males and 21 females overall), matched for sex, with an age range of 60–87 years (mean 72.3 years). Peripheral blood DNA was extracted and processed using the Illumina Infinium MethylationEPIC v2.0 BeadChip, which interrogates over 935,000 CpG sites across the genome, including promoters, enhancers, CpG islands, and other regulatory elements. The assay relies on sodium bisulfite conversion of DNA to detect methylation status at single-base resolution. Results: Epigenome-wide association study (EWAS) data allowed for multiple levels of analysis, including immune cell-type deconvolution, estimation of biological age (epigenetic clocks), quantification of stochastic epigenetic mutations (SEMs) as a measure of epigenomic stability, and differential methylation profiling. Immune cell-type inference revealed an increased but not significant proportion of monocytes in PD patients, consistent with previous reports. In contrast, epigenetic clock analysis did not reveal significant differences in biological age acceleration between cases and controls, partially at odds with earlier studies—likely due to the limited sample size. SEMs burden did not differ significantly between groups. Epivariations reveal genes involved in pathways known to be altered in dopaminergic neuron dysfunction and α-synuclein toxicity. Differential methylation analysis, however, yielded 167 CpG sites, of which 55 were located within genes, corresponding to 54 unique loci. Gene Ontology enrichment analysis highlighted significant overrepresentation of pathways with neurological relevance, including regulation of synapse structure and activity, axonogenesis, neuron migration, and synapse organization. Notably, alterations in KIAA0319, a gene involved in neuronal migration, synaptic formation, and cortical development, have previously been associated with Parkinson’s disease at the gene expression level, while methylation changes in FAM50B have been reported in neurotoxic and cognitive contexts; our data suggest, for the first time, a potential epigenetic involvement of both genes in Parkinson’s disease. Conclusions: This pilot study on a Sicilian population provides further evidence that DNA methylation profiling can yield valuable molecular insights into PD. Despite the small sample size, our results confirm previously reported findings and highlight biological pathways relevant to neuronal structure and function that may contribute to disease pathogenesis. These data support the potential of epigenetic profiling of peripheral blood as a tool to advance the understanding of PD and generate hypotheses for future large-scale studies. Full article
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