Sertad1 Plays an Essential Role in Developmentaland Pathological Neuron Death

Biswas, Subhas C.; Zhang, Yi; Iyirhiaro, Grace O.; Willett, Ryan T.; Gonzalez, Yasmilde Rodriguez; Cregan, Sean P.; Slack, Ruth S.; Park, David; Greene, Lloyd A.

doi:10.1523/jneurosci.6421-09.2010

Cited by 27 publications

(19 citation statements)

References 50 publications

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“…Rat-shParkin was generated in pSIREN vector based on the following target sequence: 5′-ATCACCTGACAGTACAGAACT -3′. Two control shRNA constructs were used: for transfection experiments, a mutant version of GATA2 silencing target sequence (Biswas et al, 2010), with no detectable homology to rodent genomic sequence, was used: 5′-GCACCTGATGTCTTCTTCAACC-3′; for lentiviral experiments, we used a mutated version of shATF4-A (mutated bases are underlined): 5′-GCC A GA T TC A GC G GC C TA C AT-3′. Rat and human ATF4 cDNAs were cloned into pCMS-eGFP, which co-expresses eGFP, for single transfection experiments, or into pcDNA3.1 for co-transfection experiments.…”

Section: Methodsmentioning

confidence: 99%

ATF4 Protects Against Neuronal Death in Cellular Parkinson's Disease Models by Maintaining Levels of Parkin

Sun¹,

Liu²,

Crary³

et al. 2013

J. Neurosci.

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112

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Parkinson’s disease (PD) is a common neurodegenerative disorder, for which there are no effective disease-modifying therapies. The transcription factor ATF4 is induced by multiple PD-relevant stressors, such as ER stress and oxidative damage. ATF4 may exert either protective or deleterious effects on cell survival, depending on the paradigm. However, the role of ATF4 in the pathogenesis of PD has not been explored. We find that ATF4 levels are increased in neuromelanin-positive neurons in the substantia nigra of a subset of Parkinson’s disease patients, relative to controls. ATF4 levels are also up-regulated in neuronal PC12 cells treated with the dopaminergic neuronal toxins toxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+). To explore the role of ATF4 in cell survival in PD-relevant contexts, we either silenced or overexpressed ATF4 in cellular models of PD. In neuronal PC12 cells, silencing of ATF4 enhanced cell death in response to either 6-OHDA or MPP+. Conversely, overexpression of ATF4 reduced cell death caused by dopaminergic neuronal toxins. ATF4 was also protective against 6-OHDA-induced death of cultured mouse ventral midbrain dopaminergic neurons. We further show that parkin, a gene associated with autosomal recessive PD, plays a critical role in ATF4-mediated protection. After treatment with 6-OHDA or MPP+, parkin protein levels fall, despite an increase in mRNA levels. ATF4 silencing exacerbates the toxin-induced reduction of parkin, while ATF4 overexpression partially preserves parkin levels. Finally, parkin silencing blocked the protective capacity of ATF4. These results indicate that ATF4 plays a protective role in Parkinson’s disease though the regulation of parkin.

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Section: Methodsmentioning

confidence: 99%

ATF4 Protects Against Neuronal Death in Cellular Parkinson's Disease Models by Maintaining Levels of Parkin

Sun¹,

Liu²,

Crary³

et al. 2013

J. Neurosci.

Self Cite

112

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“…In utero electroporation was as described in Biswas et al, 2010 except that DNA (2μg/1μl) was injected through the dorsal mesencephalon rather than telencephalon. Due to the thin lateral dimension of the mesencephalic ventricle, the capillary syringe was placed through the dorsal midline angled in the direction of the cephalic flexure.…”

Section: Methodsmentioning

confidence: 99%

Gata2 Is Required for Migration and Differentiation of Retinorecipient Neurons in the Superior Colliculus

Willett¹,

Greene²

2011

J. Neurosci.

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The superior colliculus (SC)/optic tectum of the dorsal mesencephalon plays a major role in responses to visual input, yet regulation of neuronal differentiation within this layered structure is only partially understood. Here, we show that the zinc finger transcription factor Gata2 is required for normal SC development. Starting at e15 (corresponding to the times at which neurons of the outer and intermediate layers of the SC are generated), Gata2 is transiently expressed in the rat embryonic dorsal mesencephalon within a restricted region between proliferating cells of the ventricular zone and the deepest neuronal layers of the developing SC. The Gata2 positive cells are post-mitotic and lack markers of differentiated neurons, but express markers for immature neuronal precursors including Ascl1 and Pax3/7. In utero electroporation with Gata2 shRNAs at e16 into cells along the dorsal mesencephalic ventricle interferes with their normal migration into the SC and maintains them in a state characterized by retention of Pax3 expression and the absence of mature neuronal markers. Collectively, these findings indicate that Gata2 plays a required role in the transition of post-mitotic neuronal precursor cells of the retinorecipient layers of the SC into mature neurons and that loss of Gata2 arrests them at an intermediate stage of differentiation.

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“…Cortical neurons are severely affected in AD brains and undergo death after exposure to oligomeric A␤ in vitro (5,26,28,29,(37)(38)(39). We have recently shown that the oligomeric A␤(1-42) at a concentration of 1.5 M induced significant neuron death after 24 h. Neuron death first becomes apparent by 12-16 h of A␤ exposure, and more than 40% of neurons die within 24 h (4).…”

Section: Puma Is Induced In Neurons In Response To A␤ In Cultures and Inmentioning

confidence: 99%

The Essential Role of p53-up-regulated Modulator of Apoptosis (Puma) and Its Regulation by FoxO3a Transcription Factor in β-Amyloid-induced Neuron Death

Akhter

Sanphui

Biswas

2014

Journal of Biological Chemistry

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Sertad1 Plays an Essential Role in Developmentaland Pathological Neuron Death

Cited by 27 publications

References 50 publications

ATF4 Protects Against Neuronal Death in Cellular Parkinson's Disease Models by Maintaining Levels of Parkin

ATF4 Protects Against Neuronal Death in Cellular Parkinson's Disease Models by Maintaining Levels of Parkin

Gata2 Is Required for Migration and Differentiation of Retinorecipient Neurons in the Superior Colliculus

The Essential Role of p53-up-regulated Modulator of Apoptosis (Puma) and Its Regulation by FoxO3a Transcription Factor in β-Amyloid-induced Neuron Death

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