scholarly journals Back to the future: lessons from past viral infections and the link with Parkinsons disease

2021 ◽  
Author(s):  
Declan Mckernan ◽  
Eilís Dowd
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Viral Infections ◽  
Current Knowledge ◽  
Noticeable Increase ◽  
The Future ◽  
Potential Link ◽  
The Central Nervous System ◽  
The Brain

During the current COVID-19 pandemic, there has been noticeable increase in the reporting of neurological symptoms in patients. There is still uncertainty around the significance and long-term consequence of these symptoms. There are also many outstanding questions on whether the causative virus SARS-CoV2 can directly infect the central nervous system. Given the long association between viral infections with neurodegenerative conditions such as Parkinson’s disease, it seems timely to review this literature again in the context of the COVID-19 pandemic and to glean some useful information from studies on similar viruses. In this commentary, we will consider the current knowledge on viral infections in the brain. In addition, we review the link between viral infection and neurodegeneration in Parkinson’s disease, and review the recent literature on SARS infections, the potential link with Parkinson’s disease and the potential areas of study in the future

Brain Grafting as a Treatment for Parkinson's Disease

Neurosurgery ◽  
1987 ◽  
Vol 20 (2) ◽  
pp. 335-342 ◽  
Author(s):  
Mark J. Perlow
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Manifestations ◽  
Dopamine Neurons ◽  
Clinical Aspects ◽  
Pathological Changes ◽  
Pharmacological Treatments ◽  
The Central Nervous System ◽  
The Brain

Abstract Parkinson's disease is an illness with neuropathological and neuroanatomical abnormalities in many areas of the central nervous system. Some clinical manifestations of this illness are correlated with pathological changes in the substantia nigra and with a loss of dopamine in the nigra and striatum. The most effective pharmacological treatments have used agents that either replace the lost dopamine or act as agonists on dopamine receptors. Recent studies in animal models of Parkinson's disease demonstrate that the loss of dopamine and many clinical manifestations of dopamine reduction can be reversed by transplantation of fetal dopamine-containing cells to specific dopamine-depleted areas of the brain. Long term viability of these transplants has also been demonstrated. The author suggests that the transplantation of dopamine neurons, even across species barriers, is a reasonable consideration for the treatment of human Parkinson's disease. This article reviews in detail the results of recent experiments and how the experience in these models might be utilized in determining a transplantation strategy for the treatment of specific clinical aspects of this illness.

scholarly journals Symmetric and Asymmetric Synapses Driving Neurodegenerative Disorders

Symmetry ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2333
Author(s):  
Daniel Romaus-Sanjurjo ◽  
Antía Custodia ◽  
Marta Aramburu-Núñez ◽  
Adrián Posado-Fernández ◽  
Laura Vázquez-Vázquez ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Tau Proteins ◽  
Midbrain Dopaminergic Neurons ◽  
Different Types ◽  
The Central Nervous System ◽  
First Time ◽  
The Brain

In 1959, E. G. Gray described two different types of synapses in the brain for the first time: symmetric and asymmetric. Later on, symmetric synapses were associated with inhibitory terminals, and asymmetric synapses to excitatory signaling. The balance between these two systems is critical to maintain a correct brain function. Likewise, the modulation of both types of synapses is also important to maintain a healthy equilibrium. Cerebral circuitry responds differently depending on the type of damage and the timeline of the injury. For example, promoting symmetric signaling following ischemic damage is beneficial only during the acute phase; afterwards, it further increases the initial damage. Synapses can be also altered by players not directly related to them; the chronic and long-term neurodegeneration mediated by tau proteins primarily targets asymmetric synapses by decreasing neuronal plasticity and functionality. Dopamine represents the main modulating system within the central nervous system. Indeed, the death of midbrain dopaminergic neurons impairs locomotion, underlying the devastating Parkinson’s disease. Herein, we will review studies on symmetric and asymmetric synapses plasticity after three different stressors: symmetric signaling under acute damage—ischemic stroke; asymmetric signaling under chronic and long-term neurodegeneration—Alzheimer’s disease; symmetric and asymmetric synapses without modulation—Parkinson’s disease.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

Classification of Parkinson's Disease from Smartphone Recording Data using Time-Frequency Analysis and Convolutional Neural Network (Preprint)

2021 ◽  
Author(s):  
Denchai Worasawate ◽  
Warisara Asawaponwiput ◽  
Natsue Yoshimura ◽  
Apichart Intarapanich ◽  
Decho Surangsrirat
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Fourier Transform ◽  
Short Time Fourier Transform ◽  
Time Frequency ◽  
Non Invasive ◽  
The Central Nervous System ◽  
Short Time ◽  
The Voice

BACKGROUND Parkinson’s disease (PD) is a long-term neurodegenerative disease of the central nervous system. The current diagnosis is dependent on clinical observation and the abilities and experience of a trained specialist. One of the symptoms that affect most patients over the course of their illness is voice impairment. OBJECTIVE Voice is one of the non-invasive data that can be collected remotely for diagnosis and disease progression monitoring. In this study, we analyzed voice recording data from a smartphone as a possible disease biomarker. The dataset is from one of the largest mobile PD studies, the mPower study. METHODS A total of 29,798 audio clips from 4,051 participants were used for the analysis. The voice recordings were from sustained phonation by the participant saying /aa/ for ten seconds into the iPhone microphone. The audio samples were converted to a spectrogram using a short-time Fourier transform. CNN models were then applied to classify the samples. RESULTS A total of 29,798 audio clips from 4,051 participants were used for the analysis. The voice recordings were from sustained phonation by the participant saying /aa/ for ten seconds into the iPhone microphone. The audio samples were converted to a spectrogram using a short-time Fourier transform. CNN models were then applied to classify the samples. CONCLUSIONS Classification accuracies of the proposed method with LeNet-5, ResNet-50, and VGGNet-16 are 97.7 ± 0.1%, 98.6 ± 0.2%, and 99.3 ± 0.1%, respectively. CLINICALTRIAL ClinicalTrials.gov NCT02696603; https://www.clinicaltrials.gov/ct2/show/NCT02696603

scholarly journals The Efficacy of Iron Chelators for Removing Iron from Specific Brain Regions and the Pituitary—Ironing out the Brain

2019 ◽  
Vol 12 (3) ◽  
pp. 138 ◽  
Author(s):  
Robert R. Crichton ◽  
Roberta J. Ward ◽  
Robert C. Hider
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Iron Chelation ◽  
Brain Regions ◽  
Beta Thalassemia ◽  
Excess Iron ◽  
New Class ◽  
Clinical Conditions ◽  
The Brain

Iron chelation therapy, either subcutaneous or orally administered, has been used successfully in various clinical conditions. The removal of excess iron from various tissues, e.g., the liver spleen, heart, and the pituitary, in beta thalassemia patients, has become an essential therapy to prolong life. More recently, the use of deferiprone to chelate iron from various brain regions in Parkinson’s Disease and Friederich’s Ataxia has yielded encouraging results, although the side effects, in <2% of Parkinson’s Disease(PD) patients, have limited its long-term use. A new class of hydroxpyridinones has recently been synthesised, which showed no adverse effects in preliminary trials. A vital question remaining is whether inflammation may influence chelation efficacy, with a recent study suggesting that high levels of inflammation may diminish the ability of the chelator to bind the excess iron.

scholarly journals Non-Coding RNAs in the Brain-Heart Axis: The Case of Parkinson’s Disease

2020 ◽  
Vol 21 (18) ◽  
pp. 6513 ◽  
Author(s):  
Shubhra Acharya ◽  
Antonio Salgado-Somoza ◽  
Francesca Maria Stefanizzi ◽  
Andrew I. Lumley ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Throughput ◽  
Regulatory Networks ◽  
Current Knowledge ◽  
Circular Rnas ◽  
Clinical Markers ◽  
Wide Range ◽  
Non Coding Rnas ◽  
The Brain

Parkinson’s disease (PD) is a complex and heterogeneous disorder involving multiple genetic and environmental influences. Although a wide range of PD risk factors and clinical markers for the symptomatic motor stage of the disease have been identified, there are still no reliable biomarkers available for the early pre-motor phase of PD and for predicting disease progression. High-throughput RNA-based biomarker profiling and modeling may provide a means to exploit the joint information content from a multitude of markers to derive diagnostic and prognostic signatures. In the field of PD biomarker research, currently, no clinically validated RNA-based biomarker models are available, but previous studies reported several significantly disease-associated changes in RNA abundances and activities in multiple human tissues and body fluids. Here, we review the current knowledge of the regulation and function of non-coding RNAs in PD, focusing on microRNAs, long non-coding RNAs, and circular RNAs. Since there is growing evidence for functional interactions between the heart and the brain, we discuss the benefits of studying the role of non-coding RNAs in organ interactions when deciphering the complex regulatory networks involved in PD progression. We finally review important concepts of harmonization and curation of high throughput datasets, and we discuss the potential of systems biomedicine to derive and evaluate RNA biomarker signatures from high-throughput expression data.

scholarly journals α-synuclein pathogenesis in hiPSC models of Parkinson’s Disease

2021 ◽  
Author(s):  
Leo R Quinlan ◽  
Jara Maria Baena-Montes ◽  
Sahar Avazzadeh
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Modeling ◽  
Viral Vector ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Lewy Bodies ◽  
Model Systems ◽  
The Brain

α-synuclein is an increasingly prominent player in the pathology of a variety of neurodegenerative conditions. Parkinson’s disease (PD) is a neurodegenerative disorder that affects mainly the dopaminergic neurons in the substantia nigra of the brain. Typical of PD pathology is the finding of protein aggregations termed ‘Lewy bodies’ in the brain regions affected. α-synuclein is implicated in many disease states including dementia with Lewy bodies and Alzheimer’s disease. However, PD is the most common synucleinopathy and continues to be a significant focus of PD research in terms of the α-synuclein Lewy body pathology. Mutations in several genes are associated with PD development including SNCA, which encodes α-synuclein. A variety of model systems have been employed to study α-synuclein physiology and pathophysiology in an attempt to relate more closely to PD pathology. These models include cellular and animal system exploring transgenic technologies, viral vector expression and knockdown approaches, and models to study the potential prion protein-like effects of α-synuclein. The current review focuses on human induced pluripotent stem cell (iPSC) models with a specific focus on mutations or multiplications of the SNCA gene. iPSCs are a rapidly evolving technology with huge promise in the study of normal physiology and disease modeling in vitro. The ability to maintain a patient's genetic background and replicate similar cell phenotypes make iPSCs a powerful tool in the study of neurological diseases. This review focus on the current knowledge about α-synuclein physiological function as well as its role in PD pathogenesis based on human iPSC models.

scholarly journals Knowing Your Beans in Parkinson’s Disease: A Critical Assessment of Current Knowledge about Different Beans and Their Compounds in the Treatment of Parkinson’s Disease and in Animal Models

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Michel Rijntjes
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Current Knowledge ◽  
Mucuna Pruriens ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Natural Therapy ◽  
Bioactive Ingredients

This review contains a critical appraisal of current knowledge about the use of beans in both animal models and patients with Parkinson’s disease (PD). The potential beneficial effects of beans in PD are increasingly being touted, not only in scientific journals but also by the lay media. While there is a long tradition in Ayurvedic medicine of prescribing extracts from Mucuna pruriens (MP), whose seeds contain 5% L-3,4-dihydroxyphenylalanin (L-DOPA), many other beans also contain L-DOPA (broad beans, common beans, and soybeans) or have other ingredients (coffee and cocoa) that may benefit PD patients. Indeed, bean-derived compounds can elicit neuroprotective effects in animal models of PD, while several studies in human PD patients have shown that motor performance can improve after ingestion of bean extracts. However, there are several arguments countering the view that beans serve as a natural therapy for PD: (i) the results from animal PD models are not necessarily directly applicable to humans; (ii) beans have many bioactive ingredients, some of which can be harmful in large doses; (iii) studies in human PD patients are scarce and only report on the effects of single doses or the administration of bean extract over short periods of time; and (iv) no data on long-term efficacy or side effects of bean therapy are available. Therefore, reservations about the use of beans as a “natural” therapy for PD seem to be justified.

scholarly journals Gut Microbiota and Parkinson’s Disease: Implications for Faecal Microbiota Transplantation Therapy

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110162
Author(s):  
Yongbo Kang ◽  
Xing Kang ◽  
Hongfang Zhang ◽  
Qingqing Liu ◽  
Hao Yang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Gut Microbiota ◽  
Faecal Microbiota ◽  
Faecal Microbiota Transplantation ◽  
Microbial Dysbiosis ◽  
The Future ◽  
The Central Nervous System ◽  
Microbial Strains

Parkinson's disease (PD) ranks the second place among neurodegenerative diseases in terms of its morbidity, which affects 1-2% people aged over 65 years. In addition to genetics, some environmental factors may exert vital parts in PD occurrence as well. At present, more and more studies are conducted to elucidate the association between gut microbial dysbiosis and the incidence of PD. Gut microbial dysbiosis has a certain effect on both the central nervous system (CNS) and the enteric nervous system (ENS), which indicates that there is a gut-microbiota-brain axis that induces CNS disorders. Some gut microbial strains are suggested to suppress or weaken the neuroinflammation- and gut-inflammation-immune responses, which suggests the protective and pathogenic effects of certain gut microbial species on PD progression. Therefore, gut microbiome may contain plenty of targets for preventing and managing PD. Faecal microbiota transplantation (FMT) may serve as a direct and useful treatment for PD in the future. Nonetheless, there is little available scientific research in this field. The present work reviewed the latest research to examine the association of gut microbiota with PD, and the future prospects of FMT treatment.

scholarly journals The Gut–Brain Axis and Its Relation to Parkinson’s Disease: A Review

2022 ◽  
Vol 13 ◽  
Author(s):  
Emily M. Klann ◽  
Upuli Dissanayake ◽  
Anjela Gurrala ◽  
Matthew Farrer ◽  
Aparna Wagle Shukla ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Current Knowledge ◽  
Lewy Bodies ◽  
Disease Diagnosis ◽  
Alpha Synuclein ◽  
Motor Symptoms ◽  
Abnormal Gait ◽  
Non Motor Symptoms ◽  
The Brain

Parkinson’s disease is a chronic neurodegenerative disease characterized by the accumulation of misfolded alpha-synuclein protein (Lewy bodies) in dopaminergic neurons of the substantia nigra and other related circuitry, which contribute to the development of both motor (bradykinesia, tremors, stiffness, abnormal gait) and non-motor symptoms (gastrointestinal issues, urinogenital complications, olfaction dysfunction, cognitive impairment). Despite tremendous progress in the field, the exact pathways and mechanisms responsible for the initiation and progression of this disease remain unclear. However, recent research suggests a potential relationship between the commensal gut bacteria and the brain capable of influencing neurodevelopment, brain function and health. This bidirectional communication is often referred to as the microbiome–gut–brain axis. Accumulating evidence suggests that the onset of non-motor symptoms, such as gastrointestinal manifestations, often precede the onset of motor symptoms and disease diagnosis, lending support to the potential role that the microbiome–gut–brain axis might play in the underlying pathological mechanisms of Parkinson’s disease. This review will provide an overview of and critically discuss the current knowledge of the relationship between the gut microbiota and Parkinson’s disease. We will discuss the role of α-synuclein in non-motor disease pathology, proposed pathways constituting the connection between the gut microbiome and the brain, existing evidence related to pre- and probiotic interventions. Finally, we will highlight the potential opportunity for the development of novel preventative measures and therapeutic options that could target the microbiome–gut–brain axis in the context of Parkinson’s disease.

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