scholarly journals Long-term exposure to GDNF induces dephosphorylation of Ret, AKT, and ERK1/2, and is ineffective at protecting midbrain dopaminergic neurons in cellular models of Parkinson's disease

2021 ◽  
pp. 103684
Author(s):  
V. Mesa-Infante ◽  
D. Afonso-Oramas ◽  
J. Salas-Hernández ◽  
J. Rodríguez-Núñez ◽  
P. Barroso-Chinea
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Cellular Models ◽  
Midbrain Dopaminergic Neurons

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.

scholarly journals Therapeutic Potential of Repeated Intravenous Transplantation of Human Adipose-Derived Stem Cells in Subchronic MPTP-Induced Parkinson’s Disease Mouse Model

2020 ◽  
Vol 21 (21) ◽  
pp. 8129
Author(s):  
Hyunjun Park ◽  
Keun-A Chang
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Neurodegenerative Disease ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Therapeutic Potential ◽  
Adipose Derived Stem Cells ◽  
Nigrostriatal Pathway

Parkinson’s disease (PD) is the second most common neurodegenerative disease, which is clinically and pathologically characterized by motor dysfunction and the loss of dopaminergic neurons in the substantia nigra, respectively. PD treatment with stem cells has long been studied by researchers; however, no adequate treatment strategy has been established. The results of studies so far have suggested that stem cell transplantation can be an effective treatment for PD. However, PD is a progressively deteriorating neurodegenerative disease that requires long-term treatment, and this has been insufficiently studied. Thus, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASC) for repeated vein transplantation over long-term in an animal model of PD. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice, hASCs were administered on the tail vein six times at two-week intervals. After the last injection of hASCs, motor function significantly improved. The number of dopaminergic neurons present in the nigrostriatal pathway was recovered using hASC transplantation. Moreover, the administration of hASC restored altered dopamine transporter expression and increased neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), in the striatum. Overall, this study suggests that repeated intravenous transplantation of hASC may exert therapeutic effects on PD by restoring BDNF and GDNF expressions, protecting dopaminergic neurons, and maintaining the nigrostriatal pathway.

scholarly journals Editorial for the Special Issue “Animal Models of Parkinson’s Disease and Related Disorders”

2020 ◽  
Vol 21 (12) ◽  
pp. 4250
Author(s):  
Yuzuru Imai
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Motor Dysfunction ◽  
Special Issue ◽  
Midbrain Dopaminergic Neurons ◽  
Age Dependent ◽  
Common Neurodegenerative Disorder

Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by age-dependent motor dysfunction and degeneration of the midbrain dopaminergic neurons [...]

scholarly journals STEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson’s disease

2015 ◽  
Vol 112 (4) ◽  
pp. 1202-1207 ◽  
Author(s):  
Pradeep K. Kurup ◽  
Jian Xu ◽  
Rita Alexandra Videira ◽  
Chimezie Ononenyi ◽  
Graça Baltazar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Tyrosine Phosphatase ◽  
Dopaminergic Neurons ◽  
Tyrosine Phosphatase ◽  
E3 Ligase ◽  
Substantia Nigra Pars Compacta ◽  
Rat Striatum ◽  
Protein Tyrosine ◽  
Cellular Models

Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). The loss of SNc dopaminergic neurons affects the plasticity of striatal neurons and leads to significant motor and cognitive disabilities during the progression of the disease. PARK2 encodes for the E3 ubiquitin ligase parkin and is implicated in genetic and sporadic PD. Mutations in PARK2 are a major contributing factor in the early onset of autosomal-recessive juvenile parkinsonism (AR-JP), although the mechanisms by which a disruption in parkin function contributes to the pathophysiology of PD remain unclear. Here we demonstrate that parkin is an E3 ligase for STEP61 (striatal-enriched protein tyrosine phosphatase), a protein tyrosine phosphatase implicated in several neuropsychiatric disorders. In cellular models, parkin ubiquitinates STEP61 and thereby regulates its level through the proteasome system, whereas clinically relevant parkin mutants fail to do so. STEP61 protein levels are elevated on acute down-regulation of parkin or in PARK2 KO rat striatum. Relevant to PD, STEP61 accumulates in the striatum of human sporadic PD and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mice. The increase in STEP61 is associated with a decrease in the phosphorylation of its substrate ERK1/2 and the downstream target of ERK1/2, pCREB [phospho-CREB (cAMP response element-binding protein)]. These results indicate that STEP61 is a novel substrate of parkin, although further studies are necessary to determine whether elevated STEP61 levels directly contribute to the pathophysiology of PD.

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 Short-Term GDNF Treatment Provides Long-Term Rescue of Lesioned Nigral Dopaminergic Neurons in a Rat Model of Parkinson’s Disease

1996 ◽  
Vol 16 (22) ◽  
pp. 7206-7215 ◽  
Author(s):  
Christian Winkler ◽  
Hansjörg Sauer ◽  
Chong S. Lee ◽  
Anders Björklund
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Dopaminergic Neurons ◽  
Short Term
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