α-Synuclein pathology in Drosophila melanogaster is exacerbated by haploinsufficiency of Rop: connecting STXBP1 encephalopathy with α-synucleinopathies DOI

Taro Matsuoka,

Hideki Yoshida, Takashi Kasai

et al.

Human Molecular Genetics, Journal Year: 2024, Volume and Issue: 33(15), P. 1328 - 1338

Published: May 1, 2024

Abstract Syntaxin-binding protein 1 (STXBP1) is a presynaptic that plays important roles in synaptic vesicle docking and fusion. STXBP1 haploinsufficiency causes encephalopathy (STXBP1-E), which encompasses neurological disturbances including epilepsy, neurodevelopmental disorders, movement disorders. Most patients with STXBP1-E present regression disorders adulthood, highlighting the importance of deeper understanding neurodegenerative aspects STXBP1-E. An vitro study proposed an interesting new role as molecular chaperone for α-Synuclein (αSyn), key molecule pathogenesis However, no studies have shown αSyn pathology model organisms or In this study, we used Drosophila models to examine effects on αSyn-induced neurotoxicity vivo. We demonstrated Ras opposite (Rop), ortholog STXBP1, exacerbates compound eye degeneration, locomotor dysfunction, dopaminergic neurodegeneration αSyn-expressing flies. This phenotypic aggravation was associated significant increase detergent-insoluble levels head. Furthermore, tested whether trehalose, has neuroprotective various mitigates exacerbated by Rop haploinsufficiency. flies expressing carrying heterozygous null variant, trehalose supplementation effectively alleviates neuronal phenotypes, accompanied decrease conclusion, revealed altering aggregation propensity. not only contributes mechanisms patients, but also provides insights into α-synucleinopathies.

Language: Английский

FlyBase: updates to the Drosophila genes and genomes database DOI Creative Commons
Arzu Öztürk-Çolak, Steven J Marygold, Giulia Antonazzo

et al.

Genetics, Journal Year: 2024, Volume and Issue: 227(1)

Published: Feb. 1, 2024

Abstract FlyBase (flybase.org) is a model organism database and knowledge base about Drosophila melanogaster, commonly known as the fruit fly. Researchers from around world rely on genetic, genomic, functional information available in FlyBase, well its tools to view interrogate these data. In this article, we describe latest developments updates FlyBase. These include introduction of single-cell RNA sequencing data, improved content display information, updated orthology pipelines, new chemical reports, enhancements our outreach resources.

Language: Английский

Citations

133
Integrating non-mammalian model organisms in the diagnosis of rare genetic diseases in humans DOI
Shinya Yamamoto, Oguz Kanca, Michael F. Wangler

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(1), P. 46 - 60

Published: July 25, 2023

Language: Английский

Citations

42
Drosophila functional screening of de novo variants in autism uncovers damaging variants and facilitates discovery of rare neurodevelopmental diseases DOI
Paul C. Marcogliese, Samantha L. Deal, Jonathan C. Andrews

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 38(11), P. 110517 - 110517

Published: March 1, 2022

Language: Английский

Citations

39
Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation DOI Creative Commons

Hyunglok Chung,

Qi Ye, Ye-Jin Park

et al.

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(5), P. 855 - 874.e5

Published: April 20, 2023

Language: Английский

Citations

32
Sphingolipids in neurodegenerative diseases DOI Creative Commons
Xueyang Pan, Debdeep Dutta, Shenzhao Lu

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Feb. 16, 2023

Neurodegenerative Diseases (NDDs) are a group of disorders that cause progressive deficits neuronal function. Recent evidence argues sphingolipid metabolism is affected in surprisingly broad set NDDs. These include some lysosomal storage diseases (LSDs), hereditary sensory and autonomous neuropathy (HSAN), spastic paraplegia (HSP), infantile neuroaxonal dystrophy (INAD), Friedreich’s ataxia (FRDA), as well forms amyotrophic lateral sclerosis (ALS) Parkinson’s disease (PD). Many these have been modeled Drosophila melanogaster associated with elevated levels ceramides. Similar changes also reported vertebrate cells mouse models. Here, we summarize studies using fly models and/or patient samples which demonstrate the nature defects metabolism, organelles implicated, cell types initially affected, potential therapeutics for diseases.

Language: Английский

Citations

24
Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress DOI
Lindsey D. Goodman, Isha Ralhan,

Xin Li

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(10), P. 1918 - 1933

Published: Aug. 26, 2024

Language: Английский

Citations

9
De novo variants in CDKL1 and CDKL2 are associated with neurodevelopmental symptoms DOI
Ali Hosseini Bereshneh, Jonathan C. Andrews, Daniel F. Eberl

et al.

The American Journal of Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
Drosophila melanogaster as a versatile model organism to study genetic epilepsies: An overview DOI Creative Commons
Florian P. Fischer,

Robin A. Karge,

Yvonne G. Weber

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Feb. 16, 2023

Epilepsy is one of the most prevalent neurological disorders, affecting more than 45 million people worldwide. Recent advances in genetic techniques, such as next-generation sequencing, have driven discovery and increased our understanding molecular cellular mechanisms behind many epilepsy syndromes. These insights prompt development personalized therapies tailored to characteristics an individual patient. However, surging number novel variants renders interpretation pathogenetic consequences potential therapeutic implications ever challenging. Model organisms can help explore these aspects vivo . In last decades, rodent models significantly contributed epilepsies but their establishment laborious, expensive, time-consuming. Additional model investigate disease on a large scale would be desirable. The fruit fly Drosophila melanogaster has been used organism research since “bang-sensitive” mutants half century ago. flies respond mechanical stimulation, brief vortex, with stereotypic seizures paralysis. Furthermore, identification seizure-suppressor mutations allows pinpoint targets. Gene editing CRISPR/Cas9, are convenient way generate carrying disease-associated variants. screened for phenotypic behavioral abnormalities, shifting seizure thresholds, response anti-seizure medications other substances. Moreover, modification neuronal activity induction achieved using optogenetic tools. combination calcium fluorescent imaging, functional alterations caused by genes traced. Here, we review versatile study epilepsies, especially 81% human orthologous gene discuss newly established analysis techniques that might further unravel pathophysiological epilepsies.

Language: Английский

Citations

21
Bi-allelic variants in INTS11 are associated with a complex neurological disorder DOI Creative Commons
Burak Tepe, Erica L. Macke, Marcello Niceta

et al.

The American Journal of Human Genetics, Journal Year: 2023, Volume and Issue: 110(5), P. 774 - 789

Published: April 12, 2023

Language: Английский

Citations

20
An evolutionarily conserved cation channel tunes the sensitivity of gustatory neurons to ephaptic inhibition in Drosophila DOI Creative Commons
MinHyuk Lee, Seong-min Kim,

Taeim Park

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(3)

Published: Jan. 17, 2025

In ephaptic coupling, physically adjacent neurons influence one another’s activity via the electric fields they generate. To date, molecular mechanisms that mediate and modulate coupling’s effects remain poorly understood. Here, we show hyperpolarization-activated cyclic nucleotide–gated (HCN) channel lateralizes potentially mutual inhibition between Drosophila gustatory receptor (GRNs). While sweet-sensing GRNs (sGRNs) engage in suppression of bitter-sensing (bGRNs), HCN expression sGRNs enables them to resist from bGRNs. This one-sided confers sweetness dominance, facilitating ingestion bitter-laced sweets. The role fly this process can be replaced by human HCN2. Furthermore, unlike mechanism olfaction, is independent sensillum potential changes, suggesting compartmentalized arrangement neighboring dispensable for inhibition. These findings indicate a gating coding ensure intake essential nutrient despite bitter contaminants present feeding niche , propose studies gustation could reveal principles conserved across diverse animals.

Language: Английский

Citations

0