Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
1.
Int J Mol Sci ; 23(6)2022 Mar 13.
Article in English | MEDLINE | ID: covidwho-1760647

ABSTRACT

Parkinson's disease (PD) is second-most common disabling neurological disorder worldwide, and unfortunately, there is not yet a definitive way to prevent it. Polyphenols have been widely shown protective efficacy against various PD symptoms. However, data on their effect on physio-pathological mechanisms underlying this disease are still lacking. In the present work, we evaluated the activity of a mixture of polyphenols and micronutrients, named A5+, in the murine neuroblastoma cell line N1E115 treated with 6-Hydroxydopamine (6-OHDA), an established neurotoxic stimulus used to induce an in vitro PD model. We demonstrate that a pretreatment of these cells with A5+ causes significant reduction of inflammation, resulting in a decrease in pro-inflammatory cytokines (IFN-γ, IL-6, TNF-α, and CXCL1), a reduction in ROS production and activation of extracellular signal-regulated kinases (ERK)1/2, and a decrease in apoptotic mechanisms with the related increase in cell viability. Intriguingly, A5+ treatment promoted cellular differentiation into dopaminergic neurons, as evident by the enhancement in the expression of tyrosine hydroxylase, a well-established dopaminergic neuronal marker. Overall, these results demonstrate the synergic and innovative efficacy of A5+ mixture against PD cellular pathological processes, although further studies are needed to clarify the mechanisms underlying its beneficial effect.


Subject(s)
Parkinson Disease , Animals , Disease Models, Animal , Dopaminergic Neurons/metabolism , Mice , Micronutrients/metabolism , Micronutrients/pharmacology , Micronutrients/therapeutic use , Oxidopamine/pharmacology , Parkinson Disease/drug therapy , Parkinson Disease/etiology , Parkinson Disease/metabolism , Polyphenols/metabolism , Polyphenols/pharmacology , Polyphenols/therapeutic use
2.
Mol Neurobiol ; 58(9): 4477-4486, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1241710

ABSTRACT

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of human COVID-19, not only causes flu-like symptoms and gut microbiome complications but a large number of infected individuals also experience a host of neurological symptoms including loss of smell and taste, seizures, difficulty concentrating, decreased alertness, and brain inflammation. Although SARS-CoV-2 infections are not more prevalent in Parkinson's disease patients, a higher mortality rate has been reported not only associated with older age and longer disease duration, but also through several mechanisms, such as interactions with the brain dopaminergic system and through systemic inflammatory responses. Indeed, a number of the neurological symptoms seen in COVID-19 patients, as well as the alterations in the gut microbiome, are also prevalent in patients with Parkinson's disease. Furthermore, biochemical pathways such as oxidative stress, inflammation, and protein aggregation have shared commonalities between Parkinson's disease and COVID-19 disease progression. In this review, we describe and compare the numerous similarities and intersections between neurodegeneration in Parkinson's disease and RNA viral infections, emphasizing the current SARS-CoV-2 global health crisis.


Subject(s)
COVID-19/physiopathology , Gastrointestinal Microbiome , Parkinson Disease/physiopathology , SARS-CoV-2 , Aged , COVID-19/complications , COVID-19/mortality , Cognition Disorders/etiology , Cytokines/physiology , Diet , Disease Progression , Dysbiosis/etiology , Dysbiosis/physiopathology , Humans , Inflammation , Metals, Heavy/toxicity , Models, Neurological , Nerve Degeneration , Olfactory Bulb/physiopathology , Olfactory Bulb/virology , Oxidative Stress , Parkinson Disease/etiology , Practice Guidelines as Topic , Protein Aggregation, Pathological/etiology , RNA Virus Infections/metabolism , RNA Virus Infections/physiopathology , Reactive Oxygen Species/metabolism , Sensation Disorders/etiology , alpha-Synuclein/metabolism
3.
Viruses ; 13(5)2021 05 12.
Article in English | MEDLINE | ID: covidwho-1227070

ABSTRACT

Extensive extrapulmonary damages in a dozen of organs/systems, including the central nervous system (CNS), are reported in patients of the coronavirus disease 2019 (COVID-19). Three cases of Parkinson's disease (PD) have been reported as a direct consequence of COVID-19. In spite of the scarce data for establishing a definitive link between COVID-19 and PD, some hypotheses have been proposed to explain the cases reported. They, however, do not fit well with the clinical findings reported for COVID-19 patients, in general, and for the PD cases reported, in particular. Given the importance of this potential connection, we present here a molecular-level mechanistic hypothesis that explains well these findings and will serve to explore the potential CNS damage in COVID-19 patients. The model explaining the cascade effects from COVID-19 to CNS is developed by using bioinformatic tools. It includes the post-translational modification of host proteins in the lungs by viral proteins, the transport of modified host proteins via exosomes out the lungs, and the disruption of protein-protein interaction in the CNS by these modified host proteins. Our hypothesis is supported by finding 44 proteins significantly expressed in the CNS which are associated with PD and whose interactions can be perturbed by 24 host proteins significantly expressed in the lungs. These 24 perturbators are found to interact with viral proteins and to form part of the cargoes of exosomes in human tissues. The joint set of perturbators and PD-vulnerable proteins form a tightly connected network with significantly more connections than expected by selecting a random cluster of proteins of similar size from the human proteome. The molecular-level mechanistic hypothesis presented here provides several routes for the cascading of effects from the lungs of COVID-19 patients to PD. In particular, the disruption of autophagy/ubiquitination processes appears as an important mechanism that triggers the generation of large amounts of exosomes containing perturbators in their cargo, which would insult several PD-vulnerable proteins, potentially triggering Parkinsonism in COVID-19 patients.


Subject(s)
COVID-19/complications , Parkinson Disease, Secondary/etiology , COVID-19/metabolism , Central Nervous System/virology , Exosomes/metabolism , Humans , Lung/metabolism , Models, Theoretical , Parkinson Disease/etiology , Parkinson Disease/metabolism , Parkinson Disease/virology , Parkinson Disease, Secondary/metabolism , Parkinson Disease, Secondary/virology , Protein Interaction Maps , SARS-CoV-2/pathogenicity , Viral Proteins/metabolism
4.
J Neurol Sci ; 422: 117331, 2021 03 15.
Article in English | MEDLINE | ID: covidwho-1051786
SELECTION OF CITATIONS
SEARCH DETAIL