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.

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 The immunogenicity of midbrain dopaminergic neurons and the implications for neural grafting trials in Parkinson’s disease

2021 ◽  
Author(s):  
Shamma Qarin ◽  
Sarah K Howlett ◽  
Joanne L Jones ◽  
Roger Barker
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pluripotent Stem Cells ◽  
Dopaminergic Neurons ◽  
Experimental Treatment ◽  
Safety And Efficacy ◽  
Cell Replacement ◽  
Midbrain Dopaminergic Neurons ◽  
Cell Source ◽  
Different Types

Dopaminergic (DA) cell replacement therapies are a promising experimental treatment for Parkinson’s disease and a number of different types of DA cell-based therapies have already been trialled in patients. To date the most successful have been allotransplants of foetal ventral midbrain but even then, the results have been inconsistent. This coupled to the ethical and logistical problems with using this tissue has meant that an alternative cell source has been sought of which human pluripotent stem cells (hPSC) sources have proven very attractive. Robust protocols for making mesencephalic DA progenitor cells from hPSC now exist and the first in-human clinical trials have or are about to start. However, while their safety and efficacy are well understood, relatively little is known about their immunogenicity and in this review, we briefly summarise this with reference mainly to the limited literature on human foetal dopaminergic cells.

scholarly journals Accumulation of alpha-synuclein within the liver, potential role in the clearance of brain pathology associated with Parkinson’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Juan F. Reyes ◽  
Sara Ekmark-Léwen ◽  
Marina Perdiki ◽  
Therése Klingstedt ◽  
Alana Hoffmann ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Alpha Synuclein ◽  
Wild Type ◽  
Junction Protein ◽  
The Central Nervous System ◽  
Gap Junction Protein ◽  
First Time ◽  
The Brain

AbstractAlpha-synuclein (α-syn) aggregation is the hallmark pathological lesion in brains of patients with Parkinson’s disease (PD) and related neurological disorders characterized as synucleinopathies. Accumulating evidence now indicates that α-syn deposition is also present within the gut and other peripheral organs outside the central nervous system (CNS). In the current study, we demonstrate for the first time that α-syn pathology also accumulates within the liver, the main organ responsible for substance clearance and detoxification. We further demonstrate that cultured human hepatocytes readily internalize oligomeric α-syn assemblies mediated, at least in part, by the gap junction protein connexin-32 (Cx32). Moreover, we identified a time-dependent accumulation of α-syn within the liver of three different transgenic (tg) mouse models expressing human α-syn under CNS-specific promoters, despite the lack of α-syn mRNA expression within the liver. Such a brain-to-liver transmission route could be further corroborated by detection of α-syn pathology within the liver of wild type mice one month after a single striatal α-syn injection. In contrast to the synucleinopathy models, aged mice modeling AD rarely show any amyloid-beta (Aß) deposition within the liver. In human post-mortem liver tissue, we identified cases with neuropathologically confirmed α-syn pathology containing α-syn within hepatocellular structures to a higher degree (75%) than control subjects without α-syn accumulation in the brain (57%). Our results reveal that α-syn accumulates within the liver and may be derived from the brain or other peripheral sources. Collectively, our findings indicate that the liver may play a role in the clearance and detoxification of pathological proteins in PD and related synucleinopathies.

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

scholarly journals Chronic dietary supplementation with turmeric protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-mediated neurotoxicity in vivo: implications for Parkinson's disease

2011 ◽  
Vol 106 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Rajeswara Babu Mythri ◽  
Jayagopalan Veena ◽  
G. Harish ◽  
B. S. Shankaranarayana Rao ◽  
M. M. Srinivas Bharath
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Symptomatic Relief ◽  
Dietary Supplementation ◽  
Protein Nitration ◽  
Dietary Consumption ◽  
Midbrain Dopaminergic Neurons ◽  
The Brain

Multiple pathways including oxidative stress and mitochondrial damage are implicated in neurodegeneration during Parkinson's disease (PD). The current PD drugs provide only symptomatic relief and have limitations in terms of adverse effects and inability to prevent neurodegeneration. Therefore, there is a demand for novel compound(s)/products that could target multiple pathways and protect the dying midbrain dopaminergic neurons, with potential utility as adjunctive therapy along with conventional drugs. Turmeric is a spice used in traditional Indian cuisine and medicine with antioxidant, anti-inflammatory and potential neuroprotective properties. To explore the neuroprotective property of turmeric in PD, mice were subjected to dietary supplementation with aqueous suspensions of turmeric for 3 months, mimicking its chronic consumption and challenged in vivo with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Brain samples from untreated and treated groups were characterised based on mitochondrial complex I (CI) activity, protein nitration and tyrosine hydroxylase immunoreactivity. Chronic turmeric supplementation induced the enzyme activity of γ-glutamyl cysteine ligase, which in turn increased glutathione levels and protected against peroxynitrite-mediated inhibition of brain CI. These mice were also protected against MPTP-mediated protein nitration, CI inhibition and degeneration of substantia nigra neurons in the brain. We conclude that chronic dietary consumption of turmeric protects the brain against neurotoxic insults, with potential application in neurodegeneration. Further characterisation of the active constituents of turmeric that potentially promote neuroprotection could improve the utility of dietary turmeric in brain function and disease.

Comparison of Cytocidal Activities of L-DOPA and Dopamine in S. cerevisiae and C. glabrata

2020 ◽  
Vol 16 (1) ◽  
pp. 90-93
Author(s):  
Carmen E. Iriarte ◽  
Ian G. Macreadie
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Candida Glabrata ◽  
High Sensitivity ◽  
Time Dependent ◽  
Colony Forming Units ◽  
Dependent Cell ◽  
The Brain

Background: Parkinson's Disease results from a loss of dopaminergic neurons, and reduced levels of the neurotransmitter dopamine. Parkinson's Disease treatments involve increasing dopamine levels through administration of L-DOPA, which can cross the blood brain barrier and be converted to dopamine in the brain. The toxicity of dopamine has previously studied but there has been little study of L-DOPA toxicity. Methods: We have compared the toxicity of dopamine and L-DOPA in the yeasts, Saccharomyces cerevisiae and Candida glabrata by cell viability assays, measuring colony forming units. Results: L-DOPA and dopamine caused time-dependent cell killing in Candida glabrata while only dopamine caused such effects in Saccharomyces cerevisiae. The toxicity of L-DOPA is much lower than dopamine. Conclusion: Candida glabrata exhibits high sensitivity to L-DOPA and may have advantages for studying the cytotoxicity of L-DOPA.

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

Sign in / Sign up

Export Citation Format

Share Document