DIO-SPOTlight Transgenic Mouse to Functionally Monitor Protein Synthesis Regulated by the Integrated Stress Response DOI Creative Commons
Matthew L. Oliver, Zachary F. Caffall,

Callie B Eatman

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 15, 2024

ABSTRACT The integrated stress response (ISR) is a core pathway for maintaining cellular proteostasis and key regulator of translation in processes beyond the to stress. For example, ISR regulates developmental axonogenesis, learning memory, synaptic plasticity brain. One barrier uncovering roles health disease challenge monitoring its activity. transient nature regulatory phosphorylation events lack transgenic reporter mouse lines make visually capturing molecular hallmarks activation specific cell types especially difficult. We recently developed SPOTlight ( S elective P hospho-eIF2α O pen reading frame T racking light) reporter, which uniquely provides readout functional state protein synthesis initiation dynamics that are regulated by ISR. Here, we report generation line with Cre-dependent expression SPOTlight. This resource enables selective visualization ISR-regulated activity across genetically defined populations body-wide. Using pan-neuronal Cre Nestin -Cre), demonstrate reporter’s performance applications cell-specific discovery, live tissue assessments quantitative comparisons broad physical space. also specifically investigated extent property steady-state basal activation, described dorsal striatal cholinergic interneurons, extends other classes neurons provide CNS-wide atlas these cells. DIO-SPOTlight wide range studies all organ systems opportunities not previously accessible.

Язык: Английский

DIO-SPOTlight Transgenic Mouse to Functionally Monitor Protein Synthesis Regulated by the Integrated Stress Response DOI Open Access
Matthew L. Oliver, Zachary F. Caffall,

Callie B Eatman

и другие.

Опубликована: Янв. 23, 2025

The integrated stress response (ISR) is a core pathway for maintaining cellular proteostasis and key regulator of translation in processes beyond the to stress. For example, ISR regulates developmental axonogenesis, learning memory, synaptic plasticity brain. One barrier uncovering roles health disease challenge monitoring its activity. transient nature regulatory phosphorylation events lack transgenic reporter mouse lines make visually capturing molecular hallmarks activation specific cell types especially difficult. We recently developed SPOTlight ( S elective P hospho-eIF2α O pen reading frame T racking light) reporter, which uniquely provides readout functional state protein synthesis initiation dynamics that are regulated by ISR. Here, we report generation line with Cre-dependent expression SPOTlight. This resource enables selective visualization ISR-regulated activity across genetically defined populations body-wide. Using pan-neuronal Cre Nestin -Cre), demonstrate reporter’s performance applications cell-specific discovery, live tissue assessments quantitative comparisons broad physical space. also specifically investigated extent property steady-state basal activation, described dorsal striatal cholinergic interneurons, extends other classes neurons provide CNS-wide atlas these cells. DIO-SPOTlight wide range studies all organ systems opportunities not previously accessible.

Язык: Английский

Процитировано

1
Emerging Molecular‐Genetic Families in Dystonia: Endosome‐Autophagosome‐Lysosome and Integrated Stress Response Pathways DOI Creative Commons
Nicole Calakos, Michael Zech

Movement Disorders, Год журнала: 2024, Номер unknown

Опубликована: Окт. 28, 2024

Abstract Advances in genetic technologies and disease modeling have greatly accelerated the pace of introducing validating molecular‐genetic contributors to disease. In dystonia, there is a growing convergence across multiple distinct forms onto core biological processes. Here, we discuss two these, endosome‐autophagosome‐lysosome pathway integrated stress response, highlight recent advances field. Using these pathomechanisms as examples, further opportunities that grouping dystonias present transform dystonia care. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf International Parkinson Disorder Society.

Язык: Английский

Процитировано

5
DIO-SPOTlight Transgenic Mouse to Functionally Monitor Protein Synthesis Regulated by the Integrated Stress Response DOI Open Access
Matthew L. Oliver, Zachary F. Caffall,

Callie B Eatman

и другие.

Опубликована: Янв. 23, 2025

The integrated stress response (ISR) is a core pathway for maintaining cellular proteostasis and key regulator of translation in processes beyond the to stress. For example, ISR regulates developmental axonogenesis, learning memory, synaptic plasticity brain. One barrier uncovering roles health disease challenge monitoring its activity. transient nature regulatory phosphorylation events lack transgenic reporter mouse lines make visually capturing molecular hallmarks activation specific cell types especially difficult. We recently developed SPOTlight ( S elective P hospho-eIF2α O pen reading frame T racking light) reporter, which uniquely provides readout functional state protein synthesis initiation dynamics that are regulated by ISR. Here, we report generation line with Cre-dependent expression SPOTlight. This resource enables selective visualization ISR-regulated activity across genetically defined populations body-wide. Using pan-neuronal Cre Nestin -Cre), demonstrate reporter’s performance applications cell-specific discovery, live tissue assessments quantitative comparisons broad physical space. also specifically investigated extent property steady-state basal activation, described dorsal striatal cholinergic interneurons, extends other classes neurons provide CNS-wide atlas these cells. DIO-SPOTlight wide range studies all organ systems opportunities not previously accessible.

Язык: Английский

Процитировано

0
Microglial plasticity governed by state-specific enhancer landscapes DOI Creative Commons
Nicole Hamagami,

Dvita Kapadia,

Nora Abduljawad

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

SUMMARY Single-cell transcriptomic studies have identified distinct microglial subpopulations with shared and divergent gene signatures across development, aging disease. Whether these subsets represent ontogenically separate lineages of cells, or they are manifestations plastic changes states downstream some converging signals is unknown. Furthermore, despite the well-established role enhancer landscapes underlying identity microglia, to what extent histone modifications DNA methylation regulate state switches at enhancers not been defined. Here, using genetic fate mapping, we demonstrate common embryonic origin proliferative-region-associated microglia (PAM) enriched in developing white matter, track their dynamic transitions into disease-associated (DAM) matter-associated (WAM) disease contexts, respectively. This study links spatiotemporally discrete through epigenomic plasticity, while revealing state-specific modification profiles that govern health

Язык: Английский

Процитировано

0
The integrated stress response in neurodegenerative diseases DOI Creative Commons

Maria Astrid Bravo-Jimenez,

Shivangi Sharma, Soheila Karimi‐Abdolrezaee

и другие.

Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)

Опубликована: Фев. 19, 2025

Abstract The integrated stress response (ISR) is a conserved network in eukaryotic cells that mediates adaptive responses to diverse stressors. ISR pathway ensures cell survival and homeostasis by regulating protein synthesis internal or external stresses. In recent years, the has emerged as an important regulator of central nervous system (CNS) development, pathology. Dysregulation signaling been linked several neurodegenerative diseases. Intriguingly, while acute provide neuroprotection through activation mechanisms, prolonged can promote neurodegeneration misfolding, oxidative stress, mitochondrial dysfunction. Understanding molecular mechanisms dynamics diseases aids development effective therapies. Here, we will timely review on cellular We highlight current knowledge dual role plays protective disease worsening discuss advances therapeutic approaches have developed target activity

Язык: Английский

Процитировано

0
Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: a review DOI
Maneesh Mohan, Ashi Mannan, Thakur Gurjeet Singh

и другие.

Molecular Biology Reports, Год журнала: 2025, Номер 52(1)

Опубликована: Апрель 9, 2025

Язык: Английский

Процитировано

0
Integration of omics to explore novel disease pathways in Down syndrome neurodegeneration – focusing on integrated stress response DOI Creative Commons
Beatriz Barros-Santos, Carlos Campos‐Marques, Andreia F. Salvador

и другие.

Brain Organoid and Systems Neuroscience Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Endogenous retrovirus-like proteins recruit UBQLN2 to stress granules and alter their functional properties DOI Open Access

Harihar M. Mohan,

Martín Tejedor Fernández,

Camellia Huang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 25, 2024

ABSTRACT The human genome is replete with sequences derived from foreign elements including endogenous retrovirus-like proteins of unknown function. Here we show that UBQLN2, a ubiquitin-proteasome shuttle factor implicated in neurodegenerative diseases, regulated by the linked actions two proteins, RTL8 and PEG10. confers on UBQLN2 ability to complex regulate PEG10, core component stress granules, drives recruitment granules under various conditions, but can only do so when present. Changes PEG10 levels further remodel kinetics granule disassembly overall composition incorporating select extracellular vesicle proteins. Within forms virus-like particles, underscoring structural heterogeneity this class biomolecular condensates. Together, these results reveal an unexpected link between pathways cellular proteostasis

Язык: Английский

Процитировано

1
Editorial overview: Introduction to neurobiology of disease DOI
Erik S. Musiek, Eric J. Nestler

Current Opinion in Neurobiology, Год журнала: 2024, Номер 86, С. 102875 - 102875

Опубликована: Апрель 11, 2024

Язык: Английский

Процитировано

0
DIO-SPOTlight Transgenic Mouse to Functionally Monitor Protein Synthesis Regulated by the Integrated Stress Response DOI Creative Commons
Matthew L. Oliver, Zachary F. Caffall,

Callie B Eatman

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 15, 2024

ABSTRACT The integrated stress response (ISR) is a core pathway for maintaining cellular proteostasis and key regulator of translation in processes beyond the to stress. For example, ISR regulates developmental axonogenesis, learning memory, synaptic plasticity brain. One barrier uncovering roles health disease challenge monitoring its activity. transient nature regulatory phosphorylation events lack transgenic reporter mouse lines make visually capturing molecular hallmarks activation specific cell types especially difficult. We recently developed SPOTlight ( S elective P hospho-eIF2α O pen reading frame T racking light) reporter, which uniquely provides readout functional state protein synthesis initiation dynamics that are regulated by ISR. Here, we report generation line with Cre-dependent expression SPOTlight. This resource enables selective visualization ISR-regulated activity across genetically defined populations body-wide. Using pan-neuronal Cre Nestin -Cre), demonstrate reporter’s performance applications cell-specific discovery, live tissue assessments quantitative comparisons broad physical space. also specifically investigated extent property steady-state basal activation, described dorsal striatal cholinergic interneurons, extends other classes neurons provide CNS-wide atlas these cells. DIO-SPOTlight wide range studies all organ systems opportunities not previously accessible.

Язык: Английский

Процитировано

0