Parkinson’s disease-associated Pink1 loss disrupts vesicle trafficking in Ensheathing glia causing dopaminergic neuron synapse loss

Published: Feb. 17, 2025

Parkinson’s disease (PD) is commonly associated with the loss of dopaminergic neurons in substantia nigra , but many other cell types are affected even before neuron occurs. Recent studies have linked oligodendrocytes to early stages PD, though their precise role still unclear. Pink1 mutated familial PD and through unbiased single-cell sequencing entire brain Drosophila models, we observed significant gene deregulation ensheathing glia (EG); cells that share functional similarities oligodendrocytes. We found leads activation EG, similar reactive response EG seen upon nerve injury. Using cell-type specific transcriptomics, identified deregulated genes as potential modifiers. Specifically, downregulating two trafficking factors, Rab7 Vps13, also or direct regulators Rab7, Mon1 Ccz1, specifically was sufficient rescue neuronal function protect against synapse loss. Our findings demonstrate triggers an injury turn disrupts function. Vesicle components, which regulate membrane interactions between organelles within play a crucial maintaining health preventing work highlights essential glial support pathogenesis identifies vesicle these key point convergence progression.

Language: Английский

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Parkinson’s disease-associated Pink1 loss disrupts vesicle trafficking in Ensheathing glia causing dopaminergic neuron synapse loss

Published: Feb. 17, 2025

Parkinson’s disease (PD) is commonly associated with the loss of dopaminergic neurons in substantia nigra , but many other cell types are affected even before neuron occurs. Recent studies have linked oligodendrocytes to early stages PD, though their precise role still unclear. Pink1 mutated familial PD and through unbiased single-cell sequencing entire brain Drosophila models, we observed significant gene deregulation ensheathing glia (EG); cells that share functional similarities oligodendrocytes. We found leads activation EG, similar reactive response EG seen upon nerve injury. Using cell-type specific transcriptomics, identified deregulated genes as potential modifiers. Specifically, downregulating two trafficking factors, Rab7 Vps13, also or direct regulators Rab7, Mon1 Ccz1, specifically was sufficient rescue neuronal function protect against synapse loss. Our findings demonstrate triggers an injury turn disrupts function. Vesicle components, which regulate membrane interactions between organelles within play a crucial maintaining health preventing work highlights essential glial support pathogenesis identifies vesicle these key point convergence progression.

Language: Английский

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Spatial transcriptomics in the adult Drosophila brain and body

Published: March 5, 2025

Recently, we have achieved a significant milestone with the creation of Fly Cell Atlas. This single-nuclei atlas encompasses entire fly, covering head and body, in addition to all major organs. catalogs many hundreds cell types, which annotated 250. Thus, large number clusters remain be fully characterized, particular brain. Furthermore, by applying sequencing, information about spatial location cells body possible subcellular localization mRNAs within these is lost. Spatial transcriptomics promises tackle issues. In proof-of-concept study, here applied using selected gene panel pinpoint locations 150 mRNA species adult fly. enabled us map unknown identified Atlas their fly Additionally, discovered interesting principles transcriptional diversity crowded muscle that may spark future mechanistic investigations. present set computational tools will allow for easier integration single-cell datasets.

Language: Английский

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Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 224(2)

Published: Dec. 24, 2024

Synaptic dysfunction is one of the earliest cellular defects observed in Alzheimer's disease (AD) and Parkinson's (PD), occurring before widespread protein aggregation, neuronal loss, cognitive decline. While field has focused on aggregation Tau α-Synuclein (α-Syn), emerging evidence suggests that these proteins may drive presynaptic pathology even their aggregation. Therefore, understanding mechanisms by which α-Syn affect terminals offers an opportunity for developing innovative therapeutics aimed at preserving synapses potentially halting neurodegeneration. This review focuses molecular converge caused α-Syn. Both have physiological roles synapses. However, during disease, they acquire abnormal functions due to aberrant interactions mislocalization. We provide overview current research different essential pathways influenced Finally, we highlight promising therapeutic targets maintaining synaptic function both tauopathies synucleinopathies.

Language: Английский

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Spatial transcriptomics in the adult Drosophila brain and body

Published: Jan. 17, 2024

Recently, we have achieved a significant milestone with the creation of Fly Cell Atlas. This single-nuclei atlas encompasses entire fly, covering head and body, in addition to all major organs. catalogs many hundreds cell types, which annotated 250. Thus, large number clusters remain be fully characterized, particular brain. Furthermore, by applying sequencing, information about spatial location cells body possible subcellular localization mRNAs within these is lost. Spatial transcriptomics promises tackle issues. In proof-of-concept study, here applied using selected gene panel pinpoint locations 150 mRNA species adult fly. enabled us map unknown identified Atlas their fly Additionally, discovered interesting principles transcriptional diversity crowded muscle that may spark future mechanistic investigations. present set computational tools will allow for easier integration single-cell datasets.

Language: Английский

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Parkinson's disease-associated Pink1 loss disrupts vesicle trafficking in ensheathing glia causing dopaminergic neuron synapse loss

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

ABSTRACT Parkinson’s disease (PD) is commonly associated with the loss of dopaminergic neurons in substantia nigra , but many other cell types are affected even before neuron occurs. Recent studies have linked oligodendrocytes to early stages PD, though their precise role still unclear. Pink1 mutated familial PD and through unbiased single-cell sequencing entire brain Drosophila models, we observed significant gene deregulation ensheathing glia (EG); cells that share functional similarities oligodendrocytes. We found leads activation EG, similar reactive response EG seen upon nerve injury. Using cell-type specific transcriptomics, identified deregulated genes as potential modifiers. Specifically, downregulating two trafficking factors, Rab7 Vps13, also or direct regulators Rab7, Mon1 Ccz1, specifically was sufficient rescue neuronal function protect against synapse loss. Our findings demonstrate triggers an injury turn disrupts function. Vesicle components, which regulate membrane interactions between organelles within play a crucial maintaining health preventing work highlights essential glial support pathogenesis identifies vesicle these key point convergence progression.

Language: Английский

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Spatial transcriptomics in adultDrosophilareveals new cell types in the brain and identifies subcellular mRNA patterns in muscles

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 6, 2023

Recently, we have achieved a significant milestone with the creation of Fly Cell Atlas. This single-nuclei atlas encompasses entire fly, covering head and body, in addition to all major organs. catalogs many hundreds cell types, which annotated 250. Thus, large number clusters remain be fully characterized, particular brain. Furthermore, by applying sequencing, information about spatial location cells body possible subcellular localization mRNAs within these is lost. Spatial transcriptomics promises tackle issues. In proof-of-concept study, here applied using selected gene panel pinpoint locations 150 mRNA species adult fly. enabled us map unknown identified Atlas their fly Additionally, discovered interesting principles transcriptional diversity crowded muscle that may spark future mechanistic investigations. present set computational tools will allow for easier integration single-cell datasets.

Language: Английский

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