Topics

Inactivation of hippo and cJun-N-terminal kinase (JNK) signaling mitigate FUS mediated neurodegeneration in vivo.

08:00 EDT 18th March 2020 | BioPortfolio

Summary of "Inactivation of hippo and cJun-N-terminal kinase (JNK) signaling mitigate FUS mediated neurodegeneration in vivo."

Amyotrophic Lateral Sclerosis (ALS), a late-onset neurodegenerative disorder characterized by the loss of motor neurons in the central nervous system, has no known cure to-date. Disease causing mutations in human Fused in Sarcoma (FUS) leads to aggressive and juvenile onset of ALS. FUS is a well-conserved protein across different species, which plays a crucial role in regulating different aspects of RNA metabolism. Targeted misexpression of FUS in Drosophila model recapitulates several interesting phenotypes relevant to ALS including cytoplasmic mislocalization, defects at the neuromuscular junction and motor dysfunction. We screened for the genetic modifiers of human FUS-mediated neurodegenerative phenotype using molecularly defined deficiencies. We identified hippo (hpo), a component of the evolutionarily conserved Hippo growth regulatory pathway, as a genetic modifier of FUS mediated neurodegeneration. Gain-of-function of hpo triggers cell death whereas its loss-of-function promotes cell proliferation. Downregulation of the Hippo signaling pathway, using mutants of Hippo signaling, exhibit rescue of FUS-mediated neurodegeneration in the Drosophila eye, as evident from reduction in the number of TUNEL positive nuclei as well as rescue of axonal targeting from the retina to the brain. The Hippo pathway activates c-Jun amino-terminal (NH) Kinase (JNK) mediated cell death. We found that downregulation of JNK signaling is sufficient to rescue FUS-mediated neurodegeneration in the Drosophila eye. Our study elucidates that Hippo signaling and JNK signaling are activated in response to FUS accumulation to induce neurodegeneration. These studies will shed light on the genetic mechanism involved in neurodegeneration observed in ALS and other associated disorders.

Affiliation

Journal Details

This article was published in the following journal.

Name: Neurobiology of disease
ISSN: 1095-953X
Pages: 104837

Links

DeepDyve research library

PubMed Articles [13640 Associated PubMed Articles listed on BioPortfolio]

Lola regulates adult midgut homeostasis via non-canonical Hippo signaling.

Tissue homeostasis and regeneration in the midgut is regulated by a diverse array of signaling pathways including the Hippo pathway. Hippo signaling restricts intestinal stem cell (ISC) proliferation...

PMEPA1 isoform a drives progression of glioblastoma by promoting protein degradation of the Hippo pathway kinase LATS1.

The Hippo signaling pathway controls organ development and is also known, in cancer, to have a tumor suppressing role. Within the Hippo pathway, we here demonstrate, in human gliomas, a functional int...

Kindlin-2 Inhibits the Hippo Signaling Pathway by Promoting Degradation of MOB1.

The Hippo signaling pathway plays a key role in development and cancer progression. However, molecules that intrinsically inhibit this pathway are less well known. Here, we report that the focal adhes...

Large tumor suppressor gene 2-mediated Hippo signaling pathway regulates the biological behavior of mesenchymal stem cells in vitro.

To investigate the regulatory effect of Hippo signaling pathway mediated by large tumor suppressor gene 2 (LATS2) on biological behavior of mice bone marrow mesenchymal stem cells (BMSCs) in vitro.

Activation of the intrinsic fibroinflammatory program in adult pancreatic acinar cells triggered by Hippo signaling disruption.

Damaged acinar cells play a passive role in activating pancreatic stellate cells (PSCs) via recruitment of immune cells that subsequently activate PSCs. However, whether acinar cells directly contribu...

Clinical Trials [2785 Associated Clinical Trials listed on BioPortfolio]

Hippotherapy in Children With Cerebral Palsy

The hippotherapy is a complementary therapeutic modality that seeks to promote changes in the functionality of children with cerebral palsy (CP). Knowing the domains in which this therapy ...

Effects of Weekly Hippotherapy Frequency on Children With Cerebral Palsy

The hippotherapy is considered a therapeutic modality that provides numerous benefits in the rehabilitation process and has often been recommended by doctors for children with cerebral pal...

IVM for Patients With Low Ovarian Response. Does it Improve IVFoutcomes and Does it Improve the Following IVF Cycle?

Poor ovarian response (POR) is one of the major therapeutic challenges in in vitro fertilization. Several therapeutic approaches for POR have been explored; yet, a single effective strateg...

The Activation of Hippo Pathway in Nasal Polyps

Hippo-YAP pathway is a newly discovered pathway controlling the growth, and plays important roles in the regulation of stem cell function and tissue regeneration. Previously we found that ...

Therapeutic Effects of Hippotherapy in Children With Prader-Willi Syndrome

This study evaluates the therapeutic effects of hippotherapy in children with Prader-Willi syndrome. Half of children will participate in hippotherapy for 15 weeks (30 minutes per sessions...

Medical and Biotech [MESH] Definitions

A NOD-signaling adaptor protein that contains a C-terminal leucine-rich domain which recognizes bacterial PEPTIDOGLYCAN. It signals via an N-terminal caspase recruitment domain that interacts with other CARD SIGNALING ADAPTOR PROTEINS such as RIP SERINE-THEONINE KINASES. It plays a role in the host defense response by signaling the activation of CASPASES and the MAP KINASE SIGNALING SYSTEM.

A NOD signaling adaptor protein that contains two C-terminal leucine-rich domains which recognize bacterial PEPTIDOGLYCAN. It signals via an N-terminal capase recruitment domain that interacts with other CARD SIGNALING ADAPTOR PROTEINS such as RIP SERINE-THEONINE KINASES. The protein plays a role in the host defense response by signaling the activation of CASPASES and the MAP KINASE SIGNALING SYSTEM. Mutations of the gene encoding the nucleotide oligomerization domain 2 protein have been associated with increased susceptibility to CROHN DISEASE.

A subcategory of phosphohydrolases that are specific for MITOGEN-ACTIVATED PROTEIN KINASES. They play a role in the inactivation of the MAP KINASE SIGNALING SYSTEM.

A RIP serine-theonine kinase that contains a C-terminal caspase activation and recruitment domain. It can signal by associating with other CARD-signaling adaptor proteins and INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.

A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS. The TYK2 kinase is considered the founding member of the janus kinase family and was initially discovered as a signaling partner for the INTERFERON ALPHA-BETA RECEPTOR. The kinase has since been shown to signal from several INTERLEUKIN RECEPTORS.

Quick Search


DeepDyve research library

Relevant Topic

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...


Searches Linking to this Article