ArticlePLoS genetics2018
Parallel roles of transcription factors dFOXO and FER2 in the development and maintenance of dopaminergic neurons.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 33 citations in OpenAlex.
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- Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila.Nature communications · 2023Article
- NetREX-CF integrates incomplete transcription factor data with gene expression to reconstruct gene regulatory networks.Communications biology · 2022Article
- Maintenance of mitochondrial integrity in midbrain dopaminergic neurons governed by a conserved developmental transcription factor.Nature communications · 2022Article
- A coherent FOXO3-SNAI2 feed-forward loop in autophagy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Unraveling Parkinson's Disease Neurodegeneration: Does Aging Hold the Clues?Journal of Parkinson's disease · 2022Review
- Loss of p21-activated kinase Mbt/PAK4 causes Parkinson-like phenotypes in Drosophila.Disease models & mechanisms · 2021Article
- Interactions between the microbiome and mating influence the female's transcriptional profile in Drosophila melanogaster.Scientific reports · 2020Article
- On the Fly: Recent Progress on Autophagy and Aging in Drosophila.Frontiers in cell and developmental biology · 2019Review
- Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Forkhead box (FOXO) proteins are evolutionarily conserved, stress-responsive transcription factors (TFs) that can promote or counteract cell death. Mutations in FOXO genes are implicated in numerous pathologies, including age-dependent neurodegenerative disorders, such as Parkinson's disease (PD). However, the complex regulation and downstream mechanisms of FOXOs present a challenge in understanding their roles in the pathogenesis of PD. Here, we investigate the involvement of FOXO in the death of dopaminergic (DA) neurons, the key pathological feature of PD, in Drosophila. We show that dFOXO null mutants exhibit a selective loss of DA neurons in the subgroup crucial for locomotion, the protocerebral anterior medial (PAM) cluster, during development as well as in adulthood. PAM neuron-targeted adult-restricted knockdown demonstrates that dFOXO in adult PAM neurons tissue-autonomously promotes neuronal survival during aging. We further show that dFOXO and the bHLH-TF 48-related-2 (FER2) act in parallel to protect PAM neurons from different forms of cellular stress. Remarkably, however, dFOXO and FER2 share common downstream processes leading to the regulation of autophagy and mitochondrial morphology. Thus, overexpression of one can rescue the loss of function of the other. These results indicate a role of dFOXO in neuroprotection and highlight the notion that multiple genetic and environmental factors interact to increase the risk of DA neuron degeneration and the development of PD.
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