MicroRNA-93 Blocks Signal Transducers and Activator of Transcription 3 to Reduce Neuronal Damage in Parkinson’s Disease

2021 ◽  
Author(s):  
Xiufeng Wang ◽  
Zhijun Liu ◽  
Fang Wang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Damage ◽  
Signal Transducers ◽  
Transcription 3

scholarly journals α-Synuclein, a chemoattractant, directs microglial migration via H2O2-dependent Lyn phosphorylation

2015 ◽  
Vol 112 (15) ◽  
pp. E1926-E1935 ◽  
Author(s):  
Shijun Wang ◽  
Chun-Hsien Chu ◽  
Tessandra Stewart ◽  
Carmen Ginghina ◽  
Yifei Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Migration ◽  
Neuronal Damage ◽  
Directional Migration ◽  
Chronic Neuroinflammation ◽  
Tyrosine Protein Kinase ◽  
Microglial Migration ◽  
Directional Cell Migration ◽  
Cytoskeleton Rearrangement

Malformed α-Synuclein (α-syn) aggregates in neurons are released into the extracellular space, activating microglia to induce chronic neuroinflammation that further enhances neuronal damage in α-synucleinopathies, such as Parkinson’s disease. The mechanisms by which α-syn aggregates activate and recruit microglia remain unclear, however. Here we show that α-syn aggregates act as chemoattractants to direct microglia toward damaged neurons. In addition, we describe a mechanism underlying this directional migration of microglia. Specifically, chemotaxis occurs when α-syn binds to integrin CD11b, leading to H2O2 production by NADPH oxidase. H2O2 directly attracts microglia via a process in which extracellularly generated H2O2 diffuses into the cytoplasm and tyrosine protein kinase Lyn, phosphorylates the F-actin–associated protein cortactin after sensing changes in the microglial intracellular concentration of H2O2. Finally, phosphorylated cortactin mediates actin cytoskeleton rearrangement and facilitates directional cell migration. These findings have significant implications, given that α-syn–mediated microglial migration reaches beyond Parkinson’s disease.

Emerging targets for the diagnosis of Parkinson’s disease: examination of systemic biomarkers

2021 ◽  
Author(s):  
Lara Cheslow ◽  
Adam E Snook ◽  
Scott A Waldman
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Unmet Need ◽  
Multiple Organ ◽  
The Body ◽  
Organ Systems ◽  
Diagnostic Approaches ◽  
New Biomarkers

Parkinson’s disease (PD) is a highly prevalent and irreversible neurodegenerative disorder that is typically diagnosed in an advanced stage. Currently, there are no approved biomarkers that reliably identify PD patients before they have undergone extensive neuronal damage, eliminating the opportunity for future disease-modifying therapies to intervene in disease progression. This unmet need for diagnostic and therapeutic biomarkers has fueled PD research for decades, but these efforts have not yet yielded actionable results. Recently, studies exploring mechanisms underlying PD progression have offered insights into multisystemic contributions to pathology, challenging the classic perspective of PD as a disease isolated to the brain. This shift in understanding has opened the door to potential new biomarkers from multiple sites in the body. This review focuses on emerging candidates for PD biomarkers in the context of current diagnostic approaches and multiple organ systems that contribute to disease.

scholarly journals Extracellular Vesicles in Alzheimer’s and Parkinson’s Disease: Small Entities with Large Consequences

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2485
Author(s):  
Charysse Vandendriessche ◽  
Arnout Bruggeman ◽  
Caroline Van Cauwenberghe ◽  
Roosmarijn E. Vandenbroucke
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Progression ◽  
Extracellular Vesicles ◽  
Neurodegenerative Disorders ◽  
Neuronal Damage ◽  
Protein Aggregates ◽  
Pathological Changes ◽  
Associated Proteins ◽  
The Brain

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are incurable, devastating neurodegenerative disorders characterized by the formation and spreading of protein aggregates throughout the brain. Although the exact spreading mechanism is not completely understood, extracellular vesicles (EVs) have been proposed as potential contributors. Indeed, EVs have emerged as potential carriers of disease-associated proteins and are therefore thought to play an important role in disease progression, although some beneficial functions have also been attributed to them. EVs can be isolated from a variety of sources, including biofluids, and the analysis of their content can provide a snapshot of ongoing pathological changes in the brain. This underlines their potential as biomarker candidates which is of specific relevance in AD and PD where symptoms only arise after considerable and irreversible neuronal damage has already occurred. In this review, we discuss the known beneficial and detrimental functions of EVs in AD and PD and we highlight their promising potential to be used as biomarkers in both diseases.

Neuroprotective and preventative effects of molecular hydrogen

2020 ◽  
Vol 26 ◽  
Author(s):  
Mami Noda ◽  
Jiankang Liu ◽  
Jiangang Long
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Molecular Hydrogen ◽  
Neuronal Damage ◽  
Disease Model ◽  
Endocrine System ◽  
Hydrogen Gas ◽  
Tyrosine Kinase Receptor

: One of the beneficial effects of molecular hydrogen (H2 , hydrogen gas) is neuroprotection and prevention of neurological disorders. It is important and useful if taking H2 every day can prevent or ameliorate the progression of neurodegenerative disorders such as Parkinson’s disease or Alzheimer’s disease, both lacking specific therapeutic drugs. There are several mechanisms how H2 protects neuronal damage. Anti-oxidative, anti-inflammatory, and the regulation of endocrine system via stomach-brain connection seem to play an important role. In cellular and tissue level, H2 appears to prevent the production of reactive oxygen species (ROS), not only hydroxy radical（•OH）but also superoxide. In Parkinson’s disease model mice, chronic intake of H2 causes the release of ghrelin from the stomach. In Alzheimer’s disease model mice, sex-different neuroprotection is observed by chronic intake of H2 . In female mice, declines of estrogen and estrogen receptor- (ER) are prevented by H2 , upregulating brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB). The question how drinking H2 upregulates the release of ghrelin or attenuates the decline of estrogen remains to be investigated. The mechanism how H2 modulates endocrine systems and the fundamental question what or where is the target of H2 needs to be elucidated for better understanding of the effects of H2 .

scholarly journals Deferred Administration of Afobazole Induces Sigma1R-Dependent Restoration of Striatal Dopamine Content in a Mouse Model of Parkinson’s Disease

2020 ◽  
Vol 21 (20) ◽  
pp. 7620
Author(s):  
Ilya A. Kadnikov ◽  
Ekaterina R. Verbovaya ◽  
Dmitry N. Voronkov ◽  
Mikhail V. Voronin ◽  
Sergei B. Seredenin
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Motor Behavior ◽  
Therapeutic Potential ◽  
Neuronal Damage ◽  
Selective Antagonist ◽  
Icr Mice ◽  
Selective Agonist ◽  
Dopamine Content

Previously, we demonstrated that the immediate administration of multitarget anxiolytic afobazole slows down the progression of neuronal damage in a 6-hydroxidodamine (6-OHDA) model of Parkinson’s disease due to the activation of chaperone Sigma1R. The aim of the present study is to evaluate the therapeutic potential of deferred afobazole administration in this model. Male ICR mice received a unilateral 6-OHDA lesion of the striatum. Fourteen days after the surgery, mice were treated with afobazole, selective Sigma1R agonist PRE-084, selective Sigma1R antagonist BD-1047, and a combination of BD-1047 with afobazole or PRE-084 for another 14 days. The deferred administration of afobazole restored the intrastriatal dopamine content in the 6-OHDA-lesioned striatum and facilitated motor behavior in rotarod tests. The action of afobazole accorded with the effect of Sigma1R selective agonist PRE-084 and was blocked by Sigma1R selective antagonist BD-1047. The present study illustrates the Sigma1R-dependent effects of afobazole in a 6-OHDA model of Parkinson’s disease and reveals the therapeutic potential of Sigma1R agonists in treatment of the condition.

PEP-1-PEA-15 protects against toxin-induced neuronal damage in a mouse model of Parkinson's disease

2014 ◽  
Vol 1840 (6) ◽  
pp. 1686-1700 ◽  
Author(s):  
Eun Hee Ahn ◽  
Dae Won Kim ◽  
Min Jea Shin ◽  
Hye Ri Kim ◽  
So Mi Kim ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Neuronal Damage
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