Papers > Literature on "Parkinson's Disease" in the Last Decade

Parkinson disease.

Literature Information

DOI	10.1038/nrdp.2017.13
PMID	28332488
Journal	Nature reviews. Disease primers
Impact Factor	60.6
JCR Quartile	Q1
Publication Year	2017
Times Cited	2136
Keywords	Parkinson's disease, neurodegenerative disorder, α-synuclein, motor symptoms, biomarkers
Literature Type	Journal Article, Review
ISSN	2056-676X
Pages	17013
Issue	3()
Authors	Werner Poewe, Klaus Seppi, Caroline M Tanner, Glenda M Halliday, Patrik Brundin, Jens Volkmann, Anette-Eleonore Schrag, Anthony E Lang

TL;DR

Parkinson's disease, a prevalent neurodegenerative disorder affecting older adults, is characterized by neuronal loss in the substantia nigra and α-synuclein aggregation, leading to both motor and non-motor symptoms that significantly impair quality of life. Recent advancements in neuroimaging and biomarker research aim to enhance early diagnosis and treatment strategies, highlighting the urgent need for identifying prodromal markers to facilitate the initiation of disease-modifying therapies.

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Parkinson's disease · neurodegenerative disorder · α-synuclein · motor symptoms · biomarkers

Abstract

Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.

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Primary Questions Addressed

1. What are the latest advancements in identifying prodromal stages of Parkinson disease?
2. How do non-motor symptoms of Parkinson disease impact the overall treatment strategy?
3. What role do neuroinflammation and oxidative stress play in the progression of Parkinson disease?
4. How effective are current neuroimaging techniques in differentiating Parkinson disease from other neurodegenerative disorders?
5. What are the potential benefits and challenges of gene-based and cell-based therapies for restoring striatal dopamine in Parkinson disease?

Key Findings

Background and Objectives

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting 2-3% of individuals aged 65 and older. The disease is characterized by neuronal loss in the substantia nigra, leading to dopamine deficiency, and the presence of intracellular α-synuclein aggregates. This primer aims to review the epidemiology, pathology, molecular mechanisms, clinical diagnostics, and treatment options for PD, highlighting the need for early diagnosis and disease-modifying therapies.

Main Methods/Materials/Experimental Design

The study employs a comprehensive literature review approach to analyze current understanding and advancements in Parkinson's disease. The methods include:

1. Epidemiological Studies: Data on incidence and prevalence across various demographics.
2. Pathological Studies: Examination of neuroanatomical changes and molecular pathways involved in PD.
3. Diagnostic Techniques: Utilization of neuroimaging (PET, SPECT, MRI) and genetic testing to enhance diagnostic accuracy.
4. Therapeutic Approaches: Evaluation of pharmacological and non-pharmacological interventions, including deep brain stimulation (DBS) and emerging experimental therapies.

Key Results and Findings

• Epidemiology: The incidence of PD increases significantly with age, with higher prevalence in men. Current estimates suggest a doubling of cases by 2030.
• Pathology: Key features include selective neuronal loss in the substantia nigra and the formation of Lewy bodies. The disease progresses through various stages, with α-synuclein pathology spreading from the gut and olfactory regions to the brain.
• Molecular Mechanisms: Several pathways contribute to PD pathogenesis, including mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired protein degradation.
• Diagnostics: Advances in neuroimaging and biomarker research enhance early diagnosis, though challenges remain in identifying prodromal stages.
• Therapeutic Approaches: While dopaminergic treatments like l-DOPA are effective for symptom management, they are not curative. Non-dopaminergic therapies and DBS offer additional options for managing motor and non-motor symptoms.

Main Conclusions/Significance/Innovation

Parkinson's disease is a complex disorder with multifactorial pathogenesis and significant non-motor symptoms impacting quality of life. Current treatments primarily address symptoms rather than modifying disease progression. Future research must focus on early identification of at-risk populations and the development of novel therapeutic strategies that target the underlying disease mechanisms, including immunotherapy against α-synuclein aggregates.

Limitations and Future Directions

• Limitations: The review highlights the variability in clinical presentation and progression of PD, complicating diagnosis and treatment. Additionally, the reliance on symptomatic treatments without addressing disease modification remains a significant challenge.
• Future Directions: There is a pressing need for research into biomarkers for early detection and the efficacy of disease-modifying therapies. Exploring the genetic and environmental factors influencing PD could lead to personalized treatment approaches and preventive strategies.

In summary, while significant advancements have been made in understanding and managing Parkinson's disease, continued efforts are essential to develop effective disease-modifying interventions and improve patient outcomes.

Literatures Citing This Work

1. Magnetic resonance imaging for the diagnosis of Parkinson's disease. - Beatrice Heim;Florian Krismer;Roberto De Marzi;Klaus Seppi - Journal of neural transmission (Vienna, Austria : 1996) (2017)
2. The implication of neuronimmunoendocrine (NIE) modulatory network in the pathophysiologic process of Parkinson's disease. - Yan Shen;Xingfang Guo;Chao Han;Fang Wan;Kai Ma;Shiyi Guo;Luxi Wang;Yun Xia;Ling Liu;Zhicheng Lin;Jinsha Huang;Nian Xiong;Tao Wang - Cellular and molecular life sciences : CMLS (2017)
3. Crosstalk and Interplay between the Ubiquitin-Proteasome System and Autophagy. - Chang Hoon Ji;Yong Tae Kwon - Molecules and cells (2017)
4. Progress toward an integrated understanding of Parkinson's disease. - Maxime W C Rousseaux;Joshua M Shulman;Joseph Jankovic - F1000Research (2017)
5. Mild Inflammatory Profile without Gliosis in the c-Rel Deficient Mouse Modeling a Late-Onset Parkinsonism. - Vanessa Porrini;Mariana Mota;Edoardo Parrella;Arianna Bellucci;Marina Benarese;Lara Faggi;Paolo Tonin;Pier F Spano;Marina Pizzi - Frontiers in aging neuroscience (2017)
6. Expression patterns of key Sonic Hedgehog signaling pathway components in the developing and adult mouse midbrain and in the MN9D cell line. - Melanie Feuerstein;Enaam Chleilat;Shokoufeh Khakipoor;Konstantinos Michailidis;Christian Ophoven;Eleni Roussa - Cell and tissue research (2017)
7. The Oligomer Hypothesis in α-Synucleinopathy. - Kenjiro Ono - Neurochemical research (2017)
8. Alterations in the reduced pteridine contents in the cerebrospinal fluids of LRRK2 mutation carriers and patients with Parkinson's disease. - Hiroshi Ichinose;Ken-Ichi Inoue;Shinobu Arakawa;Yuki Watanabe;Hiroki Kurosaki;Shoko Koshiba;Eldbjorg Hustad;Masahiko Takada;Jan O Aasly - Journal of neural transmission (Vienna, Austria : 1996) (2018)
9. Alpha-Synuclein to the Rescue: Immune Cell Recruitment by Alpha-Synuclein during Gastrointestinal Infection. - Viviane Labrie;Patrik Brundin - Journal of innate immunity (2017)
10. On the integrity of functional brain networks in schizophrenia, Parkinson's disease, and advanced age: Evidence from connectivity-based single-subject classification. - Rachel N Pläschke;Edna C Cieslik;Veronika I Müller;Felix Hoffstaedter;Anna Plachti;Deepthi P Varikuti;Mareike Goosses;Anne Latz;Svenja Caspers;Christiane Jockwitz;Susanne Moebus;Oliver Gruber;Claudia R Eickhoff;Kathrin Reetz;Julia Heller;Martin Südmeyer;Christian Mathys;Julian Caspers;Christian Grefkes;Tobias Kalenscher;Robert Langner;Simon B Eickhoff - Human brain mapping (2017)

... (2126 more literatures)

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