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Bipolar Disorders Jun 2020
Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Parkinson Disease; Parkinsonian Disorders
PubMed: 31954093
DOI: 10.1111/bdi.12888 -
Journal of Neural Transmission (Vienna,... Sep 2022Parkinsonism secondary to viral infections is not an uncommon occurrence and has been brought under the spotlight with the spread of severe acute respiratory syndrome... (Review)
Review
Parkinsonism secondary to viral infections is not an uncommon occurrence and has been brought under the spotlight with the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A variety of viruses have been described with a potential of inducing or contributing to the occurrence of parkinsonism and Parkinson's disease (PD), although the relationship between the two remains a matter of debate originating with the description of encephalitis lethargica in the aftermath of the Spanish flu in 1918. While some viral infections have been linked to an increased risk for the development of PD, others seem to have a causal link with the occurrence of parkinsonism. Here, we review the currently available evidence on viral-induced parkinsonism with a focus on potential pathophysiological mechanisms and clinical features. We also review the evidence on viral infections as a risk factor for developing PD and the link between SARS-CoV-2 and parkinsonism, which might have important implications for future research and treatments.
Topics: COVID-19; Humans; Influenza Pandemic, 1918-1919; Parkinson Disease; Parkinsonian Disorders; SARS-CoV-2; Virus Diseases; Viruses
PubMed: 36036863
DOI: 10.1007/s00702-022-02536-y -
International Journal of Environmental... Jul 2015Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure... (Review)
Review
Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking. In addition, we review some of the shared similarities, pathologic and clinical distinctions between Mn-induced parkinsonism and Parkinson's disease. Where possible, we review the influence of Mn toxicity on dopamine, gamma aminobutyric acid (GABA), and glutamate neurotransmitter levels and function. We conclude with a survey of the preventive and treatment strategies for manganism and idiopathic Parkinson's disease (PD).
Topics: Brain; Dopamine; Glutamic Acid; Humans; Magnesium; Manganese Poisoning; Parkinson Disease; Parkinsonian Disorders; gamma-Aminobutyric Acid
PubMed: 26154659
DOI: 10.3390/ijerph120707519 -
The Genetic Landscape of Parkinsonism-Related Dystonias and Atypical Parkinsonism-Related Syndromes.International Journal of Molecular... Jul 2021In recent decades, genetic research has nominated promising pathways and biological insights contributing to the etiological landscape of parkinsonism-related dystonias... (Review)
Review
In recent decades, genetic research has nominated promising pathways and biological insights contributing to the etiological landscape of parkinsonism-related dystonias and atypical parkinsonism-related syndromes. Several disease-causing mutations and genetic risk factors have been unraveled, providing a deeper molecular understanding of the complex genetic architecture underlying these conditions. These disorders are difficult to accurately diagnose and categorize, thus making genetics research challenging. On one hand, dystonia is an umbrella term linked to clinically heterogeneous forms of disease including dopa-responsive dystonia, myoclonus-dystonia, rapid-onset dystonia-parkinsonism and dystonia-parkinsonism, often viewed as a precursor to Parkinson's disease. On the other hand, atypical parkinsonism disorders, such as progressive supranuclear palsy, multiple system atrophy and corticobasal degeneration, are rare in nature and represent a wide range of diverse and overlapping phenotypic variabilities, with genetic research limited by sample size availability. The current review summarizes the plethora of available genetic information for these diseases, outlining limits and future directions.
Topics: Dystonia; Humans; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Supranuclear Palsy, Progressive
PubMed: 34360863
DOI: 10.3390/ijms22158100 -
Journal of Parkinson's Disease 2017
Topics: Animals; Biomedical Research; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Parkinson Disease
PubMed: 28282817
DOI: 10.3233/JPD-179008 -
Neurotherapeutics : the Journal of the... Jul 2023Ferroptosis is a programmed cell death pathway that is recently linked to Parkinson's disease (PD), where the key genes and molecules involved are still yet to be...
Ferroptosis is a programmed cell death pathway that is recently linked to Parkinson's disease (PD), where the key genes and molecules involved are still yet to be defined. Acyl-CoA synthetase long-chain family member 4 (ACSL4) esterifies polyunsaturated fatty acids (PUFAs) which is essential to trigger ferroptosis, and is suggested as a key gene in the pathogenesis of several neurological diseases including ischemic stroke and multiple sclerosis. Here, we report that ACSL4 expression in the substantia nigra (SN) was increased in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated model of PD and in dopaminergic neurons in PD patients. Knockdown of ACSL4 in the SN protected against dopaminergic neuronal death and motor deficits in the MPTP mice, while inhibition of ACSL4 activity with Triacsin C similarly ameliorated the parkinsonism phenotypes. Similar effects of ACSL4 reduction were observed in cells treated with 1-methyl-4-phenylpyridinium (MPP) and it specifically prevented the lipid ROS elevation without affecting the mitochondrial ROS changes. These data support ACSL4 as a therapeutic target associated with lipid peroxidation in PD.
Topics: Animals; Mice; Apoptosis; Dopaminergic Neurons; Lipids; Mice, Inbred C57BL; Parkinson Disease; Parkinsonian Disorders; Phenotype; Reactive Oxygen Species; Humans
PubMed: 37133631
DOI: 10.1007/s13311-023-01382-4 -
Journal of Neurology Dec 2021In March 2020, WHO declared Covid-19 outbreak pandemic. There has been increasing evidence that frail, old, multi-pathological patients are at greater risk of developing... (Review)
Review
In March 2020, WHO declared Covid-19 outbreak pandemic. There has been increasing evidence that frail, old, multi-pathological patients are at greater risk of developing severe Covid-19 infection than younger, healthy ones. Covid-19's impact on Parkinson's Disease (PD) patients could be analysed through both the influence on PD patients' health and their risk of developing severe Covid-19, and the consequences of lockdown and restrictive measures on mental and cognitive health on both patients and caregivers. Moreover, there are critical issues to be considered about patients' care and management through an unprecedented time like this. One important issue to consider is physiotherapy, as most patients cannot keep exercising because of restrictive measures which has profoundly impacted on their health. Lastly, the relationship between PD and Sars-Cov2 may be even more complicated than it seems as some studies have hypothesized a possible Covid-19-induced parkinsonism. Hereby, we review the state of the art about the relationship between Covid-19 and Parkinson's Disease, focusing on each of these five points.
Topics: COVID-19; Communicable Disease Control; Humans; Parkinson Disease; RNA, Viral; SARS-CoV-2
PubMed: 34313818
DOI: 10.1007/s00415-021-10721-4 -
Biomolecules Jul 2023Manganese (Mn) exposure has evolved from acute, high-level exposure causing manganism to low, chronic lifetime exposure. In this latter scenario, the target areas extend... (Review)
Review
Manganese (Mn) exposure has evolved from acute, high-level exposure causing manganism to low, chronic lifetime exposure. In this latter scenario, the target areas extend beyond the globus pallidus (as seen with manganism) to the entire basal ganglia, including the substantia nigra pars compacta. This change of exposure paradigm has prompted numerous epidemiological investigations of the occurrence of Parkinson's disease (PD), or parkinsonism, due to the long-term impact of Mn. In parallel, experimental research has focused on the underlying pathogenic mechanisms of Mn and its interactions with genetic susceptibility. In this review, we provide evidence from both types of studies, with the aim to link the epidemiological data with the potential mechanistic interpretation.
Topics: Humans; Manganese; Parkinsonian Disorders; Parkinson Disease; Genetic Predisposition to Disease
PubMed: 37627255
DOI: 10.3390/biom13081190 -
Journal of Parkinson's Disease 2021Parkinson's disease (PD) is thought to be caused by a combination of genetic and environmental factors. Bacterial or viral infection has been proposed as a potential... (Review)
Review
Parkinson's disease (PD) is thought to be caused by a combination of genetic and environmental factors. Bacterial or viral infection has been proposed as a potential risk factor, and there is supporting although not entirely consistent epidemiologic and basic science evidence to support its role. Encephalitis caused by influenza has included parkinsonian features. Epidemiological evidence is most compelling for an association between PD and hepatitis C virus. Infection with Helicobacter pylori may be associated not only with PD risk but also response to levodopa. Rapidly evolving knowledge regarding the role of the microbiome also suggests a role of resident bacteria in PD risk. Biological plausibility for the role for infectious agents is supported by the known neurotropic effects of specific viruses, particular vulnerability of the substantia nigra and even the promotion of aggregation of alpha-synuclein. A common feature of implicated viruses appears to be production of high levels of cytokines and chemokines that can cross the blood-brain barrier leading to microglial activation and inflammation and ultimately neuronal cell death. Based on multiple avenues of evidence it appears likely that specific bacterial and particularly viral infections may increase vulnerability to PD. The implications of this for PD prevention requires attention and may be most relevant once preventive treatments for at-risk populations are developed.
Topics: Bacterial Infections; Gastrointestinal Microbiome; Humans; Parkinson Disease; Virus Diseases
PubMed: 33361610
DOI: 10.3233/JPD-202279 -
Current Neurology and Neuroscience... Apr 2021There has been an exponential growth in functional connectomics research in neurodegenerative disorders. This review summarizes the recent findings and limitations of... (Review)
Review
PURPOSE OF REVIEW
There has been an exponential growth in functional connectomics research in neurodegenerative disorders. This review summarizes the recent findings and limitations of the field in Parkinson's disease (PD) and atypical parkinsonian syndromes.
RECENT FINDINGS
Increasingly more sophisticated methods ranging from seed-based to network and whole-brain dynamic functional connectivity have been used. Results regarding the disruption in the functional connectome vary considerably based on disease severity and phenotypes, and treatment status in PD. Non-motor symptoms of PD also link to the dysfunction in heterogeneous networks. Studies in atypical parkinsonian syndromes are relatively scarce. An important clinical goal of functional connectomics in neurodegenerative disorders is to establish the presence of pathology, track disease progression, predict outcomes, and monitor treatment response. The obstacles of reliability and reproducibility in the field need to be addressed to improve the potential of the functional connectome as a biomarker for these purposes in PD and atypical parkinsonian syndromes.
Topics: Connectome; Humans; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Reproducibility of Results; Supranuclear Palsy, Progressive
PubMed: 33817766
DOI: 10.1007/s11910-021-01111-4