Biological frameworks for Parkinson’s disease: the heterogeneity SAAgged

Journal of Neurology, Journal Year: 2025, Volume and Issue: 272(4)

Published: April 1, 2025

Language: Английский

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Optical coherence tomography reveals retinal structural abnormalities in α-synucleinopathies: insights from the Padua-CESNE cohort

Journal of Neural Transmission, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Language: Английский

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The Regional Burden of Parkinson’s Disease in Kazakhstan 2014–2021: Insights From National Health Data

Parkinson s Disease, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: This study explores the burden of Parkinson’s disease (PD) in Kazakhstan, largest country Central Asia, a region where data on neurological disorders are notably sparse. Methods: Utilizing from Kazakhstan’s Unified National Electronic Health System during 2014–2021, investigates epidemiology, disability‐adjusted life years (DALYs), and survival outcomes cohort PD patients. The authors employed Cox proportional hazards regression models Kaplan–Meier analysis, alongside sensitivity analyses, to assess impact demographic factors, hypertension, Charlson Comorbidity Index (CCI) survival. Results: included 10,125 patients, revealing tenfold increase prevalence period. Mortality rates varied significantly, with highest observed eldest age group (137.05 per 1000 person‐years). contributed loss 156.12 DALYs 100,000 population, primarily driven by lost. analysis identified an increased risk all‐cause mortality among males (adjusted hazard ratio (aHR) 1.6; 1.5–1.8), older individuals (aHR 1.05; 1.04–1.06), those higher CCIs, Kazakh ethnicity. Interestingly, patients comorbid hypertension had probability 0.67; 0.60–0.73). Conclusion: is first its kind Asia examine using large‐scale outpatient registry. findings underscore need for targeted interventions address growing PD, particularly ethnic Kazakhs. Additionally, further research needed explore inverse association between cohort.

Language: Английский

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The pharmacological management of the behavioral aspects of Parkinson’s disease: an update

Expert Opinion on Pharmacotherapy, Journal Year: 2023, Volume and Issue: 24(15), P. 1693 - 1701

Published: July 26, 2023

ABSTRACTIntroduction Behavioural symptoms are common manifestations of Parkinson’s disease and include depression, anxiety, impulse control disorders, hallucinations, psychosis, cognitive dysfunction. They remain inadequately addressed in many patients despite their relevance for quality life disability. This applies also to disorders where the most approach recent literature is refrain from using dopamine agonists without consideration about potential benefit on motor complications.Areas covered We conducted a narrative review searching articles behavioral Parkinson selected those which included involved neurotransmitters such as dopamine, noradrenaline, serotonin, acetylcholine. specifically focused our search open-label randomized double-blind studies biomarkers could best characterize these clinical manifestations.Expert opinion Management behavioural lacks clear guidelines standardized protocols beside general suggestions dose adjustments replacement therapy use antidepressants or antipsychotic drugs with little patients’ age, sex, comorbidities, status. suggest pragmatic includes education affected caring people, dealing complex cases by experienced multidisciplinary teams, therapy, psychological counselling complement drug treatment.KEYWORDS: Parkinson's DiseaseDepressionNeuropsychiatric symptomsNeuropsychiatric SymptomsAnxiety Article highlights Behavioral have profound impact well-being but especially women people non-Caucasian ethnicityMany poorly responsive dopaminergic due degeneration cholinergic, noradrenergic, serotoninergic neurotransmitter systemsAdjustments needed presence impulsive compulsive behaviors psychosis acute withdrawal medications almost invariably associated worsening increased disabilityMedications targeting non-dopaminergic systems (serotonin, noradrenaline) may improve affective symptomsA thorough neuropsychological assessment clinically significant should always be considered detect features supportive impairmentEducation well involvement an team warrantedDeclaration interestA Antonini has received compensation consultancy speaker-related activities UCB, Britannia, AbbVie, Zambon, Bial, Ever Pharma, Ferrer, Theravance Biopharma, Bayer, TreeFrog Therapeutics, Oligy, Medscape. He receives research support Horizon2020 Grant 825785, 101016902, Ministry Education University Research (MIUR) ARS01_01081, Cariparo Foundation.The authors no other relevant affiliations financial any organization entity interest conflict subject matter materials discussed manuscript apart disclosed.Reviewer disclosuresPeer reviewers this relationships disclose.Additional informationFundingThis paper was not funded.

Language: Английский

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Carboxyl truncation of α-synuclein occurs early and is influenced by human APOE genotype in transgenic mouse models of α-synuclein pathogenesis

Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)

Published: July 23, 2023

Post-translational modifications to the carboxyl (C) terminus domain of α-synuclein can play an important role in promoting pathologic aggregation α-synuclein. Various cleavages that diminish this highly charged, proline-rich region result exposure hydrophobic, aggregation-prone regions, thereby accelerating kinetics into misfolded, forms. C-terminally truncated forms are abundant human diseased brains compared controls, suggesting a disease pathogenesis. Factors alter homeostatic proteolytic processing may ultimately tip balance towards progressive state. Apolipoprotein E (APOE) has been implicated acceleration cognitive impairment patients with Lewy body diseases. The APOE4 isoform found cause dysregulation endosomal-lysosomal pathway, which could altered degradation as potential mechanism for its misfolding. Herein, we investigate spatiotemporal accumulation seeded and mouse model synucleinopathy. Furthermore, study how process is influenced context mice express either APOE3 or isoforms. We specific C-terminal truncation occurs at early stages also differs across various brain regions by presence different APOE Our data demonstrate pathogenic α-synuclein, highlight influence isoforms modulating impact.

Language: Английский

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Towards a biological diagnosis of PD

Parkinsonism & Related Disorders, Journal Year: 2024, Volume and Issue: 122, P. 106078 - 106078

Published: March 6, 2024

Since the original description by James Parkinson, Parkinson's disease (PD) has intrigued us for over 200 years. PD is a progressive condition that incurable so far, and affects millions of people worldwide. Over years, our knowledge expanded tremendously, range criteria have been put forward used to try define PD. However, owing complexity problem, it still not consensual how diagnose classify manifests with diverse features, responds differently existing therapies those under development. We are now living time when 'biological' information becoming abundant, precise, accessible enabling attempt incorporate different sources forms These refinements essential basic science, as they will enable develop improved models studying PD, implement new findings into clinical practice, this be path towards effective personalized medicine.

Language: Английский

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Rethinking Parkinson's Disease: A Syndromic Perspective

Movement Disorders, Journal Year: 2024, Volume and Issue: 39(6), P. 1079 - 1080

Published: June 1, 2024

The enigma of Parkinson's disease (PD) has long intrigued clinicians and researchers, prompting various theories explorations into its multifaceted nature. Outeiro et al recently presented an extensive review aimed at unraveling the mysteries surrounding disease.1 Their primary conclusion, based primarily on recent genetic discoveries, is that "there more than one disease." Although this important valid authors present it as a novelty, notably omitting reference to earlier work researchers who arrived similar conclusion. Donald Calne, in 1989, questioned whether singular entity article titled "Is disease?" (PMID 2).2 Calne's conclusion was unknown cause PD existence several hypothetical causes. This perspective echoed by author subsequent years, drawing accumulated information.3, 4 What even unfortunate that, despite arriving previous authors, choose not proceed with crucial next step, which involves concluding should be redefined clinical syndrome, characterized well-established features such bradykinesia, tremor, rigidity. commonality manifestations condition called actually due phenotypic convergence, akin many other disorders. Drawing parallel pneumonia, for example, my contends seen disorder composed different entities share but may have diverse causes, genetic, infectious, or toxic. There are causes including infectious dozens bacteria impossible differentiate radiological alone. However, treatment pneumonia patient requires identification causal agent. Just all patients benefit from inhaling oxygen, most find relief levodopa (l-dopa). neither oxygen nor l-dopa curative, symptom amelioration does define disease. It recognize pathology PD, deposition α-synuclein, Lewy bodies, substantia nigra degeneration, also result influenced them. Furthermore, convergence applicable only well, rendering changes like bodies nonpathognomonic, they known occur conditions. definition rely end phenotype underlying pathogenesis, core pathological process. In parkinsonism related mitochondrial damage lysosomal dysfunction, pathogenesis differs significantly therefore these diseases, if very similar. pathogenic processes cases, termed collectively "idiopathic" highlight point. Because unknown, make sense group cases single "disease." syndrome significant implications. Seeking biological markers limited usefulness because indicate late stages disease, analogous hypoxia pneumonia. Biomarkers early LRRK-2-related GBA-1 instance, until advanced stages.5 Discussing cleverly avoid implicating causative agent pathogenesis. recognizing utility marker, emphasize limitations, evidenced LRRK2- PRKN-related cases. α-synuclein deposition, therefore, pathognomonic. 2004, Calne Mizuno wrote about "The neuromythology disease," three dogmas hindering progress: "PD acceptable hallmark responsible death nigral neurons."6 Twenty years later, appears little progress been made areas, notable exception inflammatory markers. Solving riddle attempted al,1 acknowledging there no PD. We need adopt term "Parkinson's syndrome," eliminating "corticobasal ganglionic degeneration (CBG)" replacing "CBG syndrome." attempts common genetics, biomarkers, discover cure futile replaced defining subentities molecular characteristics. each subentity, additional influences, medical, environmental, present, further emphasizing move away seeking universal solution instead tailoring approaches specific subtypes.

Language: Английский

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Parkinson's Disease, Diagnosis

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

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Basic Science in Movement Disorders: Fueling the Engine of Translation into Clinical Practice

Movement Disorders, Journal Year: 2024, Volume and Issue: 39(6), P. 929 - 933

Published: April 4, 2024

Basic Science is crucial for the advancement of clinical care Movement Disorders. Here, we provide brief updates on how basic science important understanding disease mechanisms, prevention, diagnosis, development novel therapies and to establish basis personalized medicine. We conclude viewpoint by a call action further improve interactions between clinician scientists. © 2024 The Authors. Disorders published Wiley Periodicals LLC behalf International Parkinson Disorder Society.

Language: Английский

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Parkinson's Disease

Advances in medical technologies and clinical practice book series, Journal Year: 2024, Volume and Issue: unknown, P. 126 - 149

Published: Jan. 19, 2024

This chapter offers a comprehensive review of Parkinson's disease (PD), spanning from epidemiology to advanced treatment options. It delves into the neuropathology and evolution etiological theories, elucidating genetic mechanisms clinical subtypes PD. The text outlines criteria for diagnosis, including essential markers exclusion factors, while introducing innovative diagnostic frameworks. is also an integrated guide discussing future research avenues optimizing patient outcomes.

Language: Английский

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