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Over the last decades, genetics has been the engine that has pushed us along on our voyage to understand the etiology of Parkinson's disease (PD). Although a large number of risk loci and causative mutations for PD have been identified, it is clear that much more needs to be done to solve the missing heritability mystery. Despite remarkable efforts, as a field, we have failed in terms of diversity and inclusivity. The vast majority of genetic studies in PD have focused on individuals of European ancestry, leading to a gap of knowledge on the existing genetic differences across populations and PD as a whole. As we move forward, shedding light on the genetic architecture contributing to PD in non-European populations is essential, and will provide novel insight into the generalized genetic map of the disease. In this review, we discuss how better representation of understudied ancestral groups in PD genetics research requires addressing and resolving all the challenges that hinder the inclusion of these populations. We further provide an overview of PD genetics in the clinics, covering the current challenges and limitations of genetic testing and counseling. Finally, we describe the impact of worldwide collaborative initiatives in the field, shaping the future of the new era of PD genetics as we advance in our understanding of the genetic architecture of PD.
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http://dx.doi.org/10.3390/genes12111681 | DOI Listing |
Neurology
October 2025
Montreal Neurological Institute-Hospital, McGill University, Montreal, Canada.
Background And Objectives: Years before diagnosis of Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA), mild prodromal manifestations can be detected. Longitudinal follow-up of people with prodromal synucleinopathy, particularly idiopathic/isolated REM sleep behavior disorder (iRBD), enables in-depth clinical phenotyping of early disease, which could facilitate stratification for clinical trials, provide the definition of appropriate end points, or predict phenoconversion more precisely. The aim of this study was to update and expand on previous studies assessing clinical evolution from iRBD to clinically diagnosed disease, up to 14 years before diagnosis.
View Article and Find Full Text PDFJ Xray Sci Technol
September 2025
Center for Medical Artificial Intelligence, Shandong University of Traditional Chinese Medicine, Qingdao, China.
Parkinson's disease (PD) is a challenging neurodegenerative condition often prone to diagnostic errors, where early and accurate diagnosis is critical for effective clinical management. However, existing diagnostic methods often fail to fully exploit multimodal data or systematically incorporate expert domain knowledge. To address these limitations, we propose MKD-Net, a multimodal and knowledge-driven diagnostic framework that integrates imaging and non-imaging clinical data with structured expert insights to enhance diagnostic performance.
View Article and Find Full Text PDFArch Pharm Res
September 2025
College of Pharmacy, Hanyang University, Ansan, 15588, Republic of Korea.
c-Jun N-terminal kinases (JNKs), a subfamily of mitogen-activated protein kinases (MAPKs), are key mediators of cellular responses to environmental stress, inflammation, and apoptotic signals. The three isoforms-JNK1, JNK2, and JNK3 exhibit both overlapping and isoform-specific functions. While JNK1 and JNK2 are broadly expressed across tissues and regulate immune signaling, cell proliferation, and apoptosis, JNK3 expression is largely restricted to the brain, heart, and testis, where it plays a crucial role in neuronal function and survival.
View Article and Find Full Text PDFClin Auton Res
September 2025
Department of Neurology, University of Utah, Salt Lake City, UT, USA.
J Neurol
September 2025
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Background: The "Systematic Screening of Handwriting Difficulties in Parkinson's Disease" (SOS) test is the only tool specifically designed to evaluate handwriting in people with Parkinson's Disease (pwPD). It is language specific.
Objective: To assess the construct validity, intrarater and interrater reliability of the Italian version of the SOS test.