GDNF signaling in subjects with minimal motor deficits and Parkinson's disease
The failure of glial cell derived neurotropic factor to be efficacious in blinded clinical trials for Parkinson's disease may be due to alterations in signaling receptors and downstream signaling molecules. To test this hypothesis, brain sections were obtained from older adults with no motor de...
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doaj-8ac162a50392442d8d7be3e3b42470b42021-04-02T04:48:20ZengElsevierNeurobiology of Disease1095-953X2021-06-01153105298GDNF signaling in subjects with minimal motor deficits and Parkinson's diseaseYaping Chu0Jeffrey H. Kordower1Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, United States of America.Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, United States of America.; ASU-Banner Neurodgenerative Disease Research Center, Arizona State University, Tempe, Arizona 85287, United States of America.; Corresponding author at: Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison Street, Chicago, Illinois 60612, United States of America; ASU-Banner Neurodgenerative Disease Research Center, Arizona State University, Tempe, Arizona 85287, United States of America.The failure of glial cell derived neurotropic factor to be efficacious in blinded clinical trials for Parkinson's disease may be due to alterations in signaling receptors and downstream signaling molecules. To test this hypothesis, brain sections were obtained from older adults with no motor deficit (n = 6), minimal motor deficits (n = 10), and clinical diagnosis of Parkinson's disease (n = 10) who underwent motor examination proximate to death. Quantitative unbiased stereology and densitometry were performed to analyze RET and phosphorylated ribosomal protein S6 expression in nigral neurons. Individuals with no motor deficit had extensive and intense RET and phosphorylated ribosomal protein S6 immunoreactive neurons in substantia nigra. The number and staining intensity of RET-immunoreactive neurons were reduced moderately in subjects with minimal motor deficits and severely reduced in Parkinson's disease relative to no motor deficit group. The number and staining intensity of phosphorylated ribosomal protein S6 was more markedly reduced in both subjects with minimal motor deficits and Parkinson's disease. Reductions in levels of RET and phosphorylated ribosomal protein S6 were recapitulated in a non-human primate genetic Parkinson's disease model based on over-expression of human mutant α-synuclein (A53T). These data indicate that for neurotrophic factors to be effective in patients with minimal motor deficits or PD, these factors would likely have to upregulate RET and phosphorylated ribosomal protein S6 immunoreactive neurons in substantia nigra .http://www.sciencedirect.com/science/article/pii/S0969996121000474RETPhosphorylated ribosomal protein S6Dopaminergic neuronsProdromal Parkinson's disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yaping Chu Jeffrey H. Kordower |
spellingShingle |
Yaping Chu Jeffrey H. Kordower GDNF signaling in subjects with minimal motor deficits and Parkinson's disease Neurobiology of Disease RET Phosphorylated ribosomal protein S6 Dopaminergic neurons Prodromal Parkinson's disease |
author_facet |
Yaping Chu Jeffrey H. Kordower |
author_sort |
Yaping Chu |
title |
GDNF signaling in subjects with minimal motor deficits and Parkinson's disease |
title_short |
GDNF signaling in subjects with minimal motor deficits and Parkinson's disease |
title_full |
GDNF signaling in subjects with minimal motor deficits and Parkinson's disease |
title_fullStr |
GDNF signaling in subjects with minimal motor deficits and Parkinson's disease |
title_full_unstemmed |
GDNF signaling in subjects with minimal motor deficits and Parkinson's disease |
title_sort |
gdnf signaling in subjects with minimal motor deficits and parkinson's disease |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2021-06-01 |
description |
The failure of glial cell derived neurotropic factor to be efficacious in blinded clinical trials for Parkinson's disease may be due to alterations in signaling receptors and downstream signaling molecules. To test this hypothesis, brain sections were obtained from older adults with no motor deficit (n = 6), minimal motor deficits (n = 10), and clinical diagnosis of Parkinson's disease (n = 10) who underwent motor examination proximate to death. Quantitative unbiased stereology and densitometry were performed to analyze RET and phosphorylated ribosomal protein S6 expression in nigral neurons. Individuals with no motor deficit had extensive and intense RET and phosphorylated ribosomal protein S6 immunoreactive neurons in substantia nigra. The number and staining intensity of RET-immunoreactive neurons were reduced moderately in subjects with minimal motor deficits and severely reduced in Parkinson's disease relative to no motor deficit group. The number and staining intensity of phosphorylated ribosomal protein S6 was more markedly reduced in both subjects with minimal motor deficits and Parkinson's disease. Reductions in levels of RET and phosphorylated ribosomal protein S6 were recapitulated in a non-human primate genetic Parkinson's disease model based on over-expression of human mutant α-synuclein (A53T). These data indicate that for neurotrophic factors to be effective in patients with minimal motor deficits or PD, these factors would likely have to upregulate RET and phosphorylated ribosomal protein S6 immunoreactive neurons in substantia nigra . |
topic |
RET Phosphorylated ribosomal protein S6 Dopaminergic neurons Prodromal Parkinson's disease |
url |
http://www.sciencedirect.com/science/article/pii/S0969996121000474 |
work_keys_str_mv |
AT yapingchu gdnfsignalinginsubjectswithminimalmotordeficitsandparkinsonsdisease AT jeffreyhkordower gdnfsignalinginsubjectswithminimalmotordeficitsandparkinsonsdisease |
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