Unknown

Dataset Information

0

Up-regulation of activating transcription factor 4 induces severe loss of dopamine nigral neurons in a rat model of Parkinson's disease.

ABSTRACT: Activating transcription factor 4 (ATF4) is a member of the PERK signaling pathway, which directly binds endoplasmic reticulum stress target genes and plays a crucial role in both adaptations to stress and activation of apoptosis. Previous publications demonstrated conflicting evidence on the role of ATF4 in the pathogenesis of neurodegenerative disorders. In this study, we used recombinant adeno-associate virus (rAAV)-mediated gene transfer to investigate if the sustained up-regulation of ATF4 launches a pro-survival or pro-death trend in the dopamine (DA) cells of the substantia nigra pars compacta in a rat model of Parkinson-like neurodegeneration induced by human alpha-synuclein (?S) overexpression. We showed that ATF4 does not protect nigral DA neurons against an ?S-induced pathology. Moreover, the rAAV-mediated overexpression of ATF4 resulted in severe nigra-striatal degeneration via activation of caspases 3/7.

SUBMITTER: Gully JC 

PROVIDER: S-EPMC6052763 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Up-regulation of activating transcription factor 4 induces severe loss of dopamine nigral neurons in a rat model of Parkinson's disease.

Gully Joseph C JC   Sergeyev Valeriy G VG   Bhootada Yogesh Y   Mendez-Gomez Hector H   Meyers Craig A CA   Zolotukhin Sergey S   Gorbatyuk Marina S MS   Gorbatyuk Oleg S OS  

Neuroscience letters 20160524

Activating transcription factor 4 (ATF4) is a member of the PERK signaling pathway, which directly binds endoplasmic reticulum stress target genes and plays a crucial role in both adaptations to stress and activation of apoptosis. Previous publications demonstrated conflicting evidence on the role of ATF4 in the pathogenesis of neurodegenerative disorders. In this study, we used recombinant adeno-associate virus (rAAV)-mediated gene transfer to investigate if the sustained up-regulation of ATF4  ...[more]

Similar Datasets

Unknown TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF.
| S-EPMC4840550 | biostudies-literature
Unknown Delayed dominant-negative TNF gene therapy halts progressive loss of nigral dopaminergic neurons in a rat model of Parkinson's disease.
| S-EPMC3017447 | biostudies-literature
Unknown Endogenous calcium buffering capacity of substantia nigral dopamine neurons.
| S-EPMC2775382 | biostudies-other
Unknown Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss.
| S-EPMC2879040 | biostudies-other
Unknown PGC-1? activity in nigral dopamine neurons determines vulnerability to ?-synuclein.
| S-EPMC4379693 | biostudies-literature
Unknown Evidence for gender-specific transcriptional profiles of nigral dopamine neurons in Parkinson disease.
| S-EPMC2810324 | biostudies-literature
Unknown Mitochondrial DNA damage: molecular marker of vulnerable nigral neurons in Parkinson's disease.
| S-EPMC4144978 | biostudies-literature
Unknown Reversing a model of Parkinson's disease with in situ converted nigral neurons.
| S-EPMC7521455 | biostudies-literature
Unknown Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson's disease.
| S-EPMC5560326 | biostudies-other
Unknown Increased vulnerability of nigral dopamine neurons after expansion of their axonal arborization size through D2 dopamine receptor conditional knockout.
| S-EPMC6730950 | biostudies-literature