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Journal of Parkinson's Disease 2021Technology has an increasing presence and role in the management of Parkinson's disease. Whether embraced or rebuffed by patients and clinicians, this is an undoubtedly... (Review)
Review
Technology has an increasing presence and role in the management of Parkinson's disease. Whether embraced or rebuffed by patients and clinicians, this is an undoubtedly growing area. Wearable sensors have received most of the attention so far. This review will focus on technology integrated into the home setting; from fixed sensors to automated appliances, which are able to capture information and have the potential to respond in an unsupervised manner. Domotics also have the potential to provide 'real world' context to kinematic data and therapeutic opportunities to tackle challenging motor and non-motor symptoms. Together with wearable technology, domotics have the ability to gather long-term data and record discrete events, changing the model of the cross-sectional outpatient assessment. As clinicians, our ultimate goal is to maximise quality of life, promote autonomy, and personalise care. In these respects, domotics may play an essential role in the coming years.
Topics: Housing; Humans; Parkinson Disease; Technology
PubMed: 33612494
DOI: 10.3233/JPD-202398 -
Journal of Parkinson's Disease 2018Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting approximately one-percent of the population over the age of sixty. Although many...
Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting approximately one-percent of the population over the age of sixty. Although many animal models have been developed to study this disease, each model presents its own advantages and caveats. A unique model has arisen to study the role of alpha-synuclein (aSyn) in the pathogenesis of PD. This model involves the conversion of recombinant monomeric aSyn protein to a fibrillar form-the aSyn pre-formed fibril (aSyn PFF)-which is then injected into the brain or introduced to the media in culture. Although many groups have successfully adopted and replicated the aSyn PFF model, issues with generating consistent pathology have been reported by investigators. To improve the replicability of this model and diminish these issues, The Michael J. Fox Foundation for Parkinson's Research (MJFF) has enlisted the help of field leaders who performed key experiments to establish the aSyn PFF model to provide the research community with guidelines and practical tips for improving the robustness and success of this model. Specifically, we identify key pitfalls and suggestions for avoiding these mistakes as they relate to generating the aSyn PFFs from monomeric protein, validating the formation of pathogenic aSyn PFFs, and using the aSyn PFFs in vivo or in vitro to model PD. With this additional information, adoption and use of the aSyn PFF model should present fewer challenges, resulting in a robust and widely available model of PD.
Topics: Animals; Brain; Disease Models, Animal; Parkinson Disease; Rodentia; alpha-Synuclein
PubMed: 29400668
DOI: 10.3233/JPD-171248 -
Nutrients Feb 2021Methylxanthines (MTX) are purine derived xanthine derivatives. Whereas naturally occurring methylxanthines like caffeine, theophylline or theobromine are widely consumed... (Review)
Review
Methylxanthines (MTX) are purine derived xanthine derivatives. Whereas naturally occurring methylxanthines like caffeine, theophylline or theobromine are widely consumed in food, several synthetic but also non-synthetic methylxanthines are used as pharmaceuticals, in particular in treating airway constrictions. Besides the well-established bronchoprotective effects, methylxanthines are also known to have anti-inflammatory and anti-oxidative properties, mediate changes in lipid homeostasis and have neuroprotective effects. Known molecular mechanisms include adenosine receptor antagonism, phosphodiesterase inhibition, effects on the cholinergic system, wnt signaling, histone deacetylase activation and gene regulation. By affecting several pathways associated with neurodegenerative diseases via different pleiotropic mechanisms and due to its moderate side effects, intake of methylxanthines have been suggested to be an interesting approach in dealing with neurodegeneration. Especially in the past years, the impact of methylxanthines in neurodegenerative diseases has been extensively studied and several new aspects have been elucidated. In this review we summarize the findings of methylxanthines linked to Alzheimer´s disease, Parkinson's disease and Multiple Sclerosis since 2017, focusing on epidemiological and clinical studies and addressing the underlying molecular mechanisms in cell culture experiments and animal studies in order to assess the neuroprotective potential of methylxanthines in these diseases.
Topics: Alzheimer Disease; Animals; Caffeine; Coffee; Humans; Multiple Sclerosis; Neurodegenerative Diseases; Neuroprotective Agents; Parkinson Disease; Theobromine; Theophylline; Xanthines
PubMed: 33671099
DOI: 10.3390/nu13030803 -
Journal of Parkinson's Disease 2022Parkinson's disease (PD) is increasingly recognised as a systemic disorder in which inflammation might play a causative role rather than being a consequence or an... (Review)
Review
Parkinson's disease (PD) is increasingly recognised as a systemic disorder in which inflammation might play a causative role rather than being a consequence or an epiphenomenon of the neurodegenerative process. Although growing genetic evidence links the central and peripheral immune system with both monogenic and sporadic PD, our understanding on how the immune system contributes to PD pathogenesis remains a daunting challenge. In this review, we discuss recent literature aimed at exploring the role of known genes and susceptibility loci to PD pathogenesis through immune system related mechanisms. Furthermore, we outline shared genetic etiologies and interrelations between PD and autoimmune diseases and underlining challenges and limitations faced in the translation of relevant allelic and regulatory risk loci to immune-pathological mechanisms. Lastly, with the field of immunogenetics expanding rapidly, we place these insights into a future context highlighting the prospect of immune modulation as a promising disease-modifying strategy.
Topics: Causality; Humans; Immune System; Immunogenetics; Inflammation; Parkinson Disease
PubMed: 35367971
DOI: 10.3233/JPD-223176 -
Scandinavian Journal of Immunology May 2021For many years, it was postulated that the brain is the organ behind the barrier with an autonomous need for its maintenance. This view has been changed by the concept... (Review)
Review
For many years, it was postulated that the brain is the organ behind the barrier with an autonomous need for its maintenance. This view has been changed by the concept that the central nervous system is sensitive to the immune processes occurring in the periphery as well as to the infiltration of peripheral immune cells. However, how the immune system might contribute to the development of neurodegenerative diseases, such as Parkinson's disease (PD), remains unclear. PD is a chronic neurodegenerative disorder that affects motor and cognitive functions. Although the precise cause of PD is unknown, studies in both mice and human suggest that alterations in the innate immunity may play a critical role in modulating PD progression. Here, we review recent advancements in our understanding of inflammation and the innate immune mechanisms in PD pathology.
Topics: Animals; Central Nervous System; Humans; Immunity, Innate; Inflammation; Mice; Microglia; Neuroimmunomodulation; Parkinson Disease; alpha-Synuclein
PubMed: 33471378
DOI: 10.1111/sji.13022 -
Journal of Parkinson's Disease 2019The gastrointestinal (GI) tract is equipped with robust immune defenses which protect the organism from infection. Enteric nerves are front and center in this defensive... (Review)
Review
The gastrointestinal (GI) tract is equipped with robust immune defenses which protect the organism from infection. Enteric nerves are front and center in this defensive network, even in the most primitive organisms. Neuropeptides exhibit potent antimicrobial activity in the vicinity of the nerve and attract the innate and adaptive immune systems to help confine the invading agent. Alpha-synuclein (αS) has many biophysical characteristics of antimicrobial peptides and binds small vesicles such as those carrying endocytosed viruses. It is induced in nerve cells in response to viral and bacterial infections. It renders the nerve cell resistant to viral infection and propagation. It signals the immune system by attracting neutrophils and macrophages, and by activating dendritic cells. Most remarkably αS is trafficked to the central nervous system (CNS) conferring immunity in advance of an infection. Chronic GI infection or breakdown of the epithelial barrier can cause αS to accumulate and form neurotoxic aggregates. Overproduction of αS in the enteric nervous system (ENS) and its chronic trafficking to the CNS may damage nerves and lead to Parkinson's disease. Targeting the formation of αS aggregates in the ENS may therefore slow the progression of the disease.
Topics: Animals; Antimicrobial Cationic Peptides; Enteric Nervous System; Humans; Immunity; Neuropeptides; Parkinson Disease; alpha-Synuclein
PubMed: 31594249
DOI: 10.3233/JPD-191702 -
Journal of Parkinson's Disease 2015α-Synuclein is an abundant neuronal protein which localizes predominantly to presynaptic terminals, and is strongly linked genetically and pathologically to Parkinson's... (Review)
Review
α-Synuclein is an abundant neuronal protein which localizes predominantly to presynaptic terminals, and is strongly linked genetically and pathologically to Parkinson's disease and other neurodegenerative diseases. While the accumulation of α-synuclein in the form of misfolded oligomers and large aggregates defines multiple neurodegenerative diseases called "synucleinopathies", its cellular function has remained largely unclear, and is the subject of intense investigation. In this review, I focus on the structural characteristics of α-synuclein, its cellular and subcellular localization, and discuss how this relates to its function in neurons, in particular at the neuronal synapse.
Topics: Humans; Parkinson Disease; Synapses; alpha-Synuclein
PubMed: 26407041
DOI: 10.3233/JPD-150642 -
Journal of Parkinson's Disease 2018Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta, depletion of... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta, depletion of dopamine in the striatum and the presence of Lewy bodies. Cancer is uncontrolled growth of cells in the body and migration of these cells from their site of origin to other parts of the body. PD and cancer are two opposite diseases, one arising from cell proliferation and the other from cell degeneration. This fundamental difference is consistent with inverse comorbidity between most cancers and neurodegenerative diseases. However, a positive association of PD and melanoma has been reported which has recently become of significant interest. A link between PD and cancer has been supported by many epidemiological studies, most of which show that PD patients have a lower risk of developing most cancers than the general population. However, the mechanisms underlying this epidemiological observation are not known. In this review we focus on epidemiological studies correlating PD and melanoma and the possible mechanisms underlying the co-occurrence of the two diseases. We explore possible explanations for the important observations that more PD patients develop melanoma that would otherwise be expected and vice-versa.
Topics: Comorbidity; Dopaminergic Neurons; Genetic Predisposition to Disease; Humans; Melanoma; Parkinson Disease; Skin Neoplasms; Substantia Nigra
PubMed: 29991141
DOI: 10.3233/JPD-171263 -
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 -
Journal of Parkinson's Disease 2022Urinary tract infection (UTI) is a common precipitant of acute neurological deterioration in patients with Parkinson's disease (PD) and a leading cause of delirium,... (Review)
Review
Urinary tract infection (UTI) is a common precipitant of acute neurological deterioration in patients with Parkinson's disease (PD) and a leading cause of delirium, functional decline, falls, and hospitalization. Various clinical features of PD including autonomic dysfunction and altered urodynamics, frailty and cognitive impairment, and the need for bladder catheterization contribute to an increased risk of UTI. Sepsis due to UTI is a feared consequence of untreated or undertreated UTI and a leading cause of morbidity in PD. Emerging research suggests that immune-mediated brain injury may underlie the pathogenesis of UTI-induced deterioration of PD symptoms. Existing strategies to prevent UTI in patients with PD include use of topical estrogen, prophylactic supplements, antibiotic bladder irrigation, clean catheterization techniques, and prophylactic oral antibiotics, while bacterial interference and vaccines/immunostimulants directed against common UTI pathogens are potentially emerging strategies that are currently under investigation. Future research is needed to mitigate the deleterious effects of UTI in PD.
Topics: Anti-Bacterial Agents; Humans; Parkinson Disease; Urinary Tract Infections
PubMed: 35147552
DOI: 10.3233/JPD-213103