Hippo, Drosophila MST, is a novel modifier of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS

Azuma, Yumiko; Tokuda, Takahiko; Kushimura, Yukie; Yamamoto, Ikuo; Mizuta, Ikuko; Mizuno, Toshiki; Nakagawa, Masanori; Ueyama, Masashi; Nagai, Yoshitaka; Iwasaki, Yasushi; Yoshida, Mari; Pan, Duojia; Yoshida, Hideki; Yamaguchi, Masamitsu

doi:10.1016/j.yexcr.2018.08.001

Cited by 15 publications

(8 citation statements)

References 41 publications

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“…These contradictory results do not allow deciphering clearly the location (nucleus or cytoplasm, or both) where FUS induces its toxicity. Adult eclosion defect [160] No effect on lifespan, reduced mobility from young adult, decreased in total axonal branch length [150] and synaptic bouton number [177] Adult climbing defect, number of synaptic bouton and total branch length reduced [178,179] UAS-RNAi caz (1-167)…”

Section: From Fus Endogenous Functions To Toxicity 421 Nuclear and Cytoplasmic Localization Of A Shuttle Proteinmentioning

confidence: 99%

“…No effect on lifespan, reduced mobility from young adult. In larvae, decreased synaptic bouton number [150,177] Reduced synaptic projections [181] This table describes the phenotypes associated with different UAS-cabeza or UAS RNAi cabeza lines. Note that the experiments could be done at different temperatures and the UAS lines were generated using different genetic strategies (site-specific or random insertion).…”

Section: From Fus Endogenous Functions To Toxicity 421 Nuclear and Cytoplasmic Localization Of A Shuttle Proteinmentioning

confidence: 99%

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Amyotrophic Lateral Sclerosis Genes in Drosophila melanogaster

Layalle

They

Ourghani

et al. 2021

IJMS

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Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disease characterized by the progressive degeneration of upper and lower motoneurons. Most ALS cases are sporadic but approximately 10% of ALS cases are due to inherited mutations in identified genes. ALS-causing mutations were identified in over 30 genes with superoxide dismutase-1 (SOD1), chromosome 9 open reading frame 72 (C9orf72), fused in sarcoma (FUS), and TAR DNA-binding protein (TARDBP, encoding TDP-43) being the most frequent. In the last few decades, Drosophila melanogaster emerged as a versatile model for studying neurodegenerative diseases, including ALS. In this review, we describe the different Drosophila ALS models that have been successfully used to decipher the cellular and molecular pathways associated with SOD1, C9orf72, FUS, and TDP-43. The study of the known fruit fly orthologs of these ALS-related genes yielded significant insights into cellular mechanisms and physiological functions. Moreover, genetic screening in tissue-specific gain-of-function mutants that mimic ALS-associated phenotypes identified disease-modifying genes. Here, we propose a comprehensive review on the Drosophila research focused on four ALS-linked genes that has revealed novel pathogenic mechanisms and identified potential therapeutic targets for future therapy.

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Section: From Fus Endogenous Functions To Toxicity 421 Nuclear and Cytoplasmic Localization Of A Shuttle Proteinmentioning

confidence: 99%

Section: From Fus Endogenous Functions To Toxicity 421 Nuclear and Cytoplasmic Localization Of A Shuttle Proteinmentioning

confidence: 99%

Amyotrophic Lateral Sclerosis Genes in Drosophila melanogaster

Layalle

They

Ourghani

et al. 2021

IJMS

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“…But full‐length YAP and activated p73 level were found to be preserved until the late symptomatic stage, suggesting YAP–p73‐mediated transcriptional dysregulation as a crucial mechanism for neuronal death in ALS (Morimoto et al, ). In a recent study, MST1 homolog Hpo has been identified as a key modulator of neurodegeneration in a transgenic Drosophila ALS model (Azuma et al, ). In G93ASOD1 transgenic mice model for ALS, MST1‐mediated activation of the p38‐MAPK pathway is reported.…”

Section: Disease Implications Of the Hyperactivated Hippo Pathwaymentioning

confidence: 99%

“…In a Caz (the drosophila ortholog of human fused in Sarcoma [FUS]) knockdown Drosophila model of ALS, loss of function mutation in the Hippo/hpo gene was found to reinstate the reduced Caz levels in the eye. Also, hpo mutation meliorated the aberrant compound eye morphology and restored neuronal‐specific deficits caused by Caz knockdown (Azuma et al, ). Genetic deficiency of MST1 has also shown to be neuroprotective that delays the disease onset and extends neuronal survival in a transgenic mice model for ALS (Lee et al, ).…”

Section: Disease Implications Of the Hyperactivated Hippo Pathwaymentioning

confidence: 99%

“…It is characterized by progressive loss of upper and lower motor neurons at the spinal or bulbar level (Rowland & Shneider, ). Hippo pathway alteration‐induced neuronal death has been reported in the pathogenesis of ALS in various systems ranging from transgenic Drosophila ALS model to human ALS patient brains (Azuma et al, ; Lee et al, ; Morimoto et al, ). Similar to the findings on relevance of TRAID to HD, TRAID was also found to be involved in ALS pathophysiology.…”

Section: Disease Implications Of the Hyperactivated Hippo Pathwaymentioning

confidence: 99%

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The emerging role of Hippo signaling in neurodegeneration

Sahu

Mondal

2019

J of Neuroscience Research

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Neurodegeneration refers to the complex process of progressive degeneration or neuronal apoptosis leading to a set of incurable and debilitating conditions. Physiologically, apoptosis is important in proper growth and development. However, aberrant and unrestricted apoptosis can lead to a variety of degenerative conditions including neurodegenerative diseases. Although dysregulated apoptosis has been implicated in various neurodegenerative disorders, the triggers and molecular mechanisms underlying such untimely and faulty apoptosis are still unknown. Hippo signaling pathway is one such apoptosis‐regulating mechanism that has remained evolutionarily conserved from Drosophila to mammals. This pathway has gained a lot of attention for its tumor‐suppressing task, but recent studies have emphasized the soaring role of this pathway in inflaming neurodegeneration. In addition, strategies promoting inactivation of this pathway have aided in the rescue of neurons from anomalous apoptosis. So, a thorough understanding of the relationship between the Hippo pathway and neurodegeneration may serve as a guide for the development of therapy for various degenerative diseases. The current review focuses on the mechanism of the Hippo signaling pathway, its upstream and downstream regulatory molecules, and its role in the genesis of numerous neurodegenerative diseases. The recent efforts employing the Hippo pathway components as targets for checking neurodegeneration have also been highlighted.

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