scholarly journals Repressing PTB is incapable to convert reactive astrocytes to dopaminergic neurons in a mouse model of Parkinson's disease

2021 ◽  
Author(s):  
Weizhao Chen ◽  
Qiongping Zheng ◽  
Qiaoying Huang ◽  
Shanshan Ma ◽  
Mingtao Li
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Lineage Tracing ◽  
Reactive Astrocytes ◽  
Reactive Astrocyte ◽  
Adeno Associated Virus ◽  
Polypyrimidine Tract Binding Protein ◽  
Tracing Method

Lineage reprograming of resident glia cells to induced dopaminergic neurons (iDAns) holds attractive prospect for cell-replacement therapy of Parkinson's disease (PD). Recently, whether repressing polypyrimidine tract binding protein (PTB) could truly achieve efficient astrocyte-to-iDAn conversion in substantia nigra and striatum aroused widespread controversy. Although reporter+ iDAns were observed by two groups after delivering adeno-associated virus (AAV) expressing a reporter with shRNA or Crispr-CasRx to repress astroglial PTB, the possibility of AAV leaking into endogenous DAns could not be excluded without using a reliable lineage tracing method. By adopting stringent lineage tracing strategy, two other studies showed that neither knockdown nor genetic deletion of quiescent astroglial PTB fails to obtain iDAns under physiological condition. However, the role of reactive astrocyte might be underestimated since upon brain injury, reactive astrocyte could acquire certain stem cell hallmarks which may facilitate the lineage conversion process. Therefore, whether reactive astrocytes could be genuinely converted to DAns after PTB repression in a PD model needs further validation. In this study, we used Aldh1l1-CreERT2-mediated specific astrocyte-lineage tracing method to investigate whether reactive astrocytes could be converted to DAns in the 6-OHDA PD model. However, we found that no astrocyte-originated DAns was generated after effective knockdown of astroglial PTB either in the substantia nigra or in the striatum, while AAV leakage to nearby neurons was observed. Our results further confirmed that repressing PTB is unable to convert astrocytes to DA neurons no matter in physiological or PD-related pathological conditions.

Low Levels of Prohibitin in Substantia Nigra Makes Dopaminergic Neurons Vulnerable in Parkinson’s Disease

2017 ◽  
Vol 55 (1) ◽  
pp. 804-821 ◽  
Author(s):  
Debashis Dutta ◽  
Nilufar Ali ◽  
Emili Banerjee ◽  
Raghavendra Singh ◽  
Amit Naskar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Low Levels

Parkinson's Disease

2019 ◽  
pp. 252-273 ◽  
Author(s):  
Vaibhav Walia ◽  
Ashish Gakkhar ◽  
Munish Garg
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Older Patients ◽  
Neurodegenerative Disorder ◽  
Progressive Loss ◽  
The Brain

Parkinson's disease (PD) is a neurodegenerative disorder in which a progressive loss of the dopaminergic neurons occurs. The loss of the neurons is most prominent in the substantia nigra region of the brain. The prevalence of PD is much greater among the older patients suggesting the risk of PD increases with the increase of age. The exact cause of the neurodegeneration in PD is not known. In this chapter, the authors introduce PD, demonstrate its history, pathogenesis, neurobiology, sign and symptoms, diagnosis, and pharmacotherapy.

Neurotoxicity risk assessment of MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) as a synthetic impurity of drugs

1998 ◽  
Vol 17 (5) ◽  
pp. 283-293 ◽  
Author(s):  
Peter Juergen Kramer ◽  
John Caldwell ◽  
Andreas Hofmann ◽  
Peter Tempel ◽  
Guenter Weisse
Keyword(s):  
Risk Assessment ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Health Risk ◽  
Globus Pallidus ◽  
Dopaminergic Neurons ◽  
Idiopathic Parkinson's Disease ◽  
Candidate Drug ◽  
A Minor

1-Methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) induces symptoms indistinguishable from those of Parkinson's disease. It selectively destroys dopaminergic neurons in the substantia nigra and the globus pallidus. Death of these same neurons is apparently the cause of idiopathic Parkinson's disease. As phenyl-1,2,3,6 tetrahydropyridine is a commonly encountered subunit in heterocyclic drugs and because MPTP was found as a minor impurity in early batches of a candidate drug at Merck KGaA, it may be assumed that MPTP will also be present as an as yet undiscovered minor impurity in various existing drugs. A neurotoxicity risk assessment on MPTP has been conducted to define the risk of MPTP as an impurity in drugs that are used orally. This risk assessment has shown that compounds containing less than 5.0 p.p.m. MPTP administered orally will not cause a neurotoxicological health risk to patients treated with such a drug.

Protective effects of fisetin and other berry flavonoids in Parkinson's disease

2017 ◽  
Vol 8 (9) ◽  
pp. 3033-3042 ◽  
Author(s):  
Pamela Maher
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Degenerative Disease ◽  
Protective Effects

Parkinson's disease (PD) is an age-associated degenerative disease of the midbrain that results from the loss of dopaminergic neurons in the substantia nigra.

scholarly journals Autophagin-3 (ATG4C) is differentially expressed in the brains of patients with Parkinson’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Differentially Expressed ◽  
Gene Encoding ◽  
Microarray Datasets

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published microarray datasets (2, 3) to identify genes whose expression was most different in the substantial nigra of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding autophagin-3 (ATG4C) in the substantia nigra of patients with PD.

scholarly journals Role of Genes and Treatments for Parkinson’s Disease

2020 ◽  
Vol 8 (1) ◽  
pp. 47-65
Author(s):  
Falaq Naz ◽  
Yasir Hasan Siddique
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Autosomal Dominant ◽  
Neurodegenerative Disorder ◽  
Treatment Strategies ◽  
Number Of Genes ◽  
Permanent Cure

Parkinson’s Disease (PD) is a complex neurodegenerative disorder that mainly results due to the loss of dopaminergic neurons in the substantia nigra of the midbrain. It is well known that dopamine is synthesized in substantia nigra and is transported to the striatum via nigrostriatal tract. Besides the sporadic forms of PD, there are also familial cases of PD and number of genes (both autosomal dominant as well as recessive) are responsible for PD. There is no permanent cure for PD and to date, L-dopa therapy is considered to be the best option besides having dopamine agonists. In the present review, we have described the genes responsible for PD, the role of dopamine, and treatment strategies adopted for controlling the progression of PD in humans.

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