SEARCHNARRATIVE_REVIEWneurology, preclinical research

narrative_review·neurology, preclinical research, biomedical research, geriatrics·PMC10601631

Parkinson’s Disease: A Tale of Many Players

Medical Principles and Practice · 2 authors, 2 centres

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This narrative review discusses the epidemiology, neuropathology, and therapeutic research landscape of Parkinson's disease (PD).

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This narrative review discusses the epidemiology, neuropathology, and therapeutic research landscape of Parkinson's disease (PD). It describes PD as a global health burden, noting a 2020 prevalence of over 9 million patients and projections for substantial growth. The review details core pathological features, including the loss of dopaminergic neurons and the presence of Lewy bodies containing alpha-synuclein. The narrative highlights recent research on novel biomarkers, specifically an alpha-synuclein seeding assay with high diagnostic sensitivity and specificity, and gut microbiome associations. It also reviews emerging therapeutic avenues, such as physical activity, cell-based therapies, and genetic approaches like CRISPR/Cas9. Implications suggest promising directions for early diagnosis and disease modification.

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narrative_review

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neurology

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ORIGINAL PAPER

PMC10601631

Parkinson’s Disease: A Tale of Many Players

Medical Principles and Practice

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ABSTRACT

Abstract In 2020, more than 9 million patients suffering from Parkinson’s disease (PD) were reported worldwide, and studies predict that the burden of this disease will grow substantially in industrial countries. In the last decade, there has been a better understanding of this neurodegenerative disorder, clinically characterized by motor disturbances, impaired balance, coordination, memory difficulties, and behavioral changes. Various preclinical investigations and studies on human postmortem brains suggest that local oxidative stress and inflammation promote misfolding and aggregation of alpha-synuclein within Lewy bodies and cause nerve cell damage. Parallel to these investigations, the familial contribution to the disease became evident from studies on genome-wide association in which specific genetic defects were linked to neuritic alpha-synuclein pathology. As for treatment, currently available pharmacological and surgical interventions may improve the quality of life but do not stop the progress of neurodegeneration. However, numerous preclinical studies have provided insights into the pathogenesis of PD. Their results provide a solid base for clinical trials and further developments. In this review, we discuss the pathogenesis, the prospects, and challenges of synolytic therapy, CRISPR, gene editing, and gene- and cell-based therapy. We also throw light on the recent observation that targeted physiotherapy may help improve the gait and other motor impairments. Keywords: Parkinson’s disease, Alpha-synuclein, Synolytics, Cell-based therapy, Targeted physiotherapy

CITATION EXPORT

Ernest K J Pauwels, Gerard J Boer. Parkinson’s Disease: A Tale of Many Players. Medical Principles and Practice. (2023). https://doi.org/10.1159/000531422

AUTHORS

2 · 2 CENTRES

Ernest K J Pauwels, Gerard J Boer

aLeiden University and Leiden University Medical Center, Leiden, The Netherlands
bNetherlands Institute for Brain Research, Royal Academy of Arts and Sciences, Amsterdam, The Netherlands