Tau reduction impairs nephrocyte function in Drosophila.

Tau, a microtubule-associated protein, is known for its significant involvement in neurodegenerative diseases. While various molecular and immunohistochemical techniques have confirmed the presence of Tau in podocytes, its precise function within these cells remains elusive. In this study, we investigate the role of Tau in kidney podocytes using Drosophila pericardial nephrocytes as a model.

Knockdown of glutathione S-transferase leads to mislocalization and accumulation of cabeza, a homolog of FUS, in the brain.

Glutathione S-transferase omega (GSTO) is an antioxidant enzyme involved in reducing oxidative stress. Recent studies suggest that polymorphic variants of GSTOs affect the onset age and progression of neurodegenerative diseases. Although GSTO activity may affect the development and age dependency of several diseases, the mechanism by which GSTO inactivation in neurons regulates the susceptibility to neurodegenerative diseases is unclear.

Therapeutic modulation of GSTO activity rescues FUS-associated neurotoxicity via deglutathionylation in ALS disease models.

Fused in sarcoma (FUS) is a DNA/RNA-binding protein that is involved in DNA repair and RNA processing. FUS is associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the molecular mechanisms underlying FUS-mediated neurodegeneration are largely unknown.

Effects of the Edaravone, a Drug Approved for the Treatment of Amyotrophic Lateral Sclerosis, on Mitochondrial Function and Neuroprotection.

Edaravone, the first known free radical scavenger, has demonstrated cellular protective properties in animals and humans. Owing to its antioxidant activity, edaravone modulates oxidative damage in various diseases, especially neurodegenerative diseases. In 2015, edaravone was approved in Japan to treat amyotrophic lateral sclerosis.

FUS-induced neurotoxicity is prevented by inhibiting GSK-3β in a Drosophila model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS)-linked mutations in fused in sarcoma (FUS) lead to the formation of cytoplasmic aggregates in neurons. They are believed to play a critical role in the pathogenesis of FUS-associated ALS. Therefore, the clearance and degradation of cytoplasmic FUS aggregates in neurons may be considered a therapeutic strategy for ALS.

Dysfunction of Mitochondrial Dynamics in Model of Diabetic Nephropathy.

Although mitochondrial dysfunction is associated with the development and progression of diabetic nephropathy (DN), its mechanisms are poorly understood, and it remains debatable whether mitochondrial morphological change is a cause of DN. In this study, a DN model was established by treating a chronic high-sucrose diet that exhibits similar phenotypes in animals. Results showed that flies fed a chronic high-sucrose diet exhibited a reduction in lifespan, as well as increased lipid droplets in fat body tissue.

Recent Advances on the Role of GSK3β in the Pathogenesis of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease characterized by progressive motor neuron degeneration. Although several studies on genes involved in ALS have substantially expanded and improved our understanding of ALS pathogenesis, the exact molecular mechanisms underlying this disease remain poorly understood. Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine-protein kinase that plays a critical role in the regulation of various cellular signaling pathways.

SCF-Slimb is critical for Glycogen synthase kinase-3β-mediated suppression of TAF15-induced neurotoxicity in Drosophila.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder characterized pathologically by motor neuron degeneration and associated with aggregation of RNA-binding proteins. TATA-binding protein-associated factor 15 (TAF15) accumulates as cytoplasmic aggregates in neuronal cells, and clearance of these aggregates is considered a potential therapeutic strategy for ALS. However, the exact pathogenic mechanism of TAF15-induced neurotoxicity remains to be elucidated.

Glutathione S-Transferase Rescues Motor Neuronal Toxicity in Fly Model of Amyotrophic Lateral Sclerosis.

Transactive response DNA-binding protein-43 (TDP-43) is involved in the pathology of familial and sporadic amyotrophic lateral sclerosis (ALS). TDP-43-mediated ALS models in mice, , and zebrafish exhibit dysfunction of locomotor function, defective neuromuscular junctions, and motor neuron defects. There is currently no effective cure for ALS, and the underlying mechanisms of TDP-43 in ALS remain poorly understood.

PERK-Mediated eIF2α Phosphorylation Contributes to The Protection of Dopaminergic Neurons from Chronic Heat Stress in .

Environmental high-temperature heat exposure is linked to physiological stress such as disturbed protein homeostasis caused by endoplasmic reticulum (ER) stress. Abnormal proteostasis in neuronal cells is a common pathological factor of Parkinson's disease (PD). Chronic heat stress is thought to induce neuronal cell death during the onset and progression of PD, but the exact role and mechanism of ER stress and the activation of the unfolded protein response (UPR) remains unclear.

The Model: Exploring Novel Therapeutic Compounds against Neurodegenerative Diseases.

Polyphenols are secondary metabolites of plants, fruits, and vegetables. They act as antioxidants against free radicals from UV light, pathogens, parasites, and oxidative stress. In models, feeding with various polyphenols results in increased antioxidant capacity and prolonged lifespan.

PTK2/FAK regulates UPS impairment via SQSTM1/p62 phosphorylation in TARDBP/TDP-43 proteinopathies.

TARDBP/TDP-43 (TAR DNA binding protein) proteinopathies are a common feature in a variety of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and Alzheimer disease (AD). However, the molecular mechanisms underlying TARDBP-induced neurotoxicity are largely unknown. In this study, we demonstrated that TARDBP proteinopathies induce impairment in the ubiquitin proteasome system (UPS), as evidenced by an accumulation of ubiquitinated proteins and a reduction in proteasome activity in neuronal cells.

Genetic activation of parkin rescues TAF15-induced neurotoxicity in a Drosophila model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder that is characterized pathologically by the loss of motor neurons. Mutations in the TAF15 gene have been implicated in the pathogenesis of ALS. TATA-binding protein associated factor 15 (TAF15) accumulates as cytoplasmic aggregates in neuronal cells, the clearance of which may be a therapeutic strategy for ALS.

Protein Glutathionylation in the Pathogenesis of Neurodegenerative Diseases.

Protein glutathionylation is a redox-mediated posttranslational modification that regulates the function of target proteins by conjugating glutathione with a cysteine thiol group on the target proteins. Protein glutathionylation has several biological functions such as regulation of metabolic pathways, calcium homeostasis, signal transduction, remodeling of cytoskeleton, inflammation, and protein folding. However, the exact role and mechanism of glutathionylation during irreversible oxidative stress has not been completely defined.

Omega Class Glutathione S-Transferase: Antioxidant Enzyme in Pathogenesis of Neurodegenerative Diseases.

The omega class glutathione S-transferases (GSTOs) are multifunctional enzymes involved in cellular defense and have distinct structural and functional characteristics, which differ from those of other GSTs. Previous studies provided evidence for the neuroprotective effects of GSTOs. However, the molecular mechanisms underpinning the neuroprotective functions of GSTOs have not been fully elucidated.

Imbalance of mitochondrial dynamics in Drosophila models of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease, characterized by progressive and selective loss of motor neurons in the brain and spinal cord. DNA/RNA-binding proteins such as TDP-43, FUS, and TAF15 have been linked with the sporadic and familial forms of ALS. However, the exact pathogenic mechanism of ALS is still unknown.

Protective effect of Drosophila glutathione transferase omega 1 against hydrogen peroxide-induced neuronal toxicity.

Glutathione transferase omega (GSTO) belongs to a recently identified family of glutathione transferase (GST) and presents several known functions. In Drosophila, despite the high sequence identity among the four GstO isoforms, they present different physiological functions. Herein, we showed that GstO1, which is one of the Drosophila GstOs, is highly expressed in adult heads.