Complex Regulation of Tau Phosphorylation by the Endothelin System in Brain Microvascular Endothelial Cells (BMVECs): Link to Barrier Function DOI Creative Commons
Eda Karakaya, Yasir Abdul, Jazlyn Edwards

et al.

Clinical Science, Journal Year: 2024, Volume and Issue: 138(21), P. 1329 - 1341

Published: Oct. 2, 2024

Endothelin-1 (ET-1), the most potent vasoconstrictor identified to date, contributes cerebrovascular dysfunction. ET-1 levels in postmortem brain specimens from individuals diagnosed with Alzheimer's disease (AD) and related dementias (ADRD) were shown be cerebral hypoxia severity. ET-1-mediated vascular dysfunction ensuing cognitive deficits have also been reported experimental models of AD ADRD. Moreover, studies showed that secreted microvascular endothelial cells (BMVECs) can affect neurovascular unit integrity an autocrine paracrine manner. Vascular contributions impairment dementia (VCID) is a leading ADRD cause known free neuronal tau pathology, hallmark AD. However, recent study cytotoxic hyperphosphorylated (p-tau) accumulation, which fails bind or stabilize microtubules BMVECs VCID. Thus, aimed determine impact on microtubule organization, barrier function BMVECs. Cells stimulated 1 μM for 24 h presence/absence ETA (BQ123; 20 μM) ETB (BQ788; receptor antagonists. Cell lysates assayed array phosphorylation site-specific antibodies organization/stabilization markers. stimulation increased p-tau Thr231 but decreased Ser199, Ser262, Ser396, Ser214 only presence antagonism. impaired These novel findings suggest (1) dysregulation may contribute (2) ET system early intervention target prevent tau-mediated disruption BMVEC function.

Language: Английский

Seeding-competent early tau multimers are associated with cell type-specific transcriptional signatures DOI Creative Commons
Rahel Feleke,

Simona Jogaudaite,

Elisavet Velentza‐Almpani

et al.

Acta Neuropathologica, Journal Year: 2025, Volume and Issue: 149(1)

Published: April 4, 2025

Language: Английский

Citations

0
The interactome of tau phosphorylated at T217 in Alzheimer’s disease human brain tissue DOI Creative Commons
Tomas Kavanagh,

Manon Thierry,

Kaleah Balcomb

et al.

Acta Neuropathologica, Journal Year: 2025, Volume and Issue: 149(1)

Published: May 3, 2025

Abstract Hyperphosphorylated tau (pTau) in Alzheimer’s disease (AD) brain tissue is a complex mix of multiple species that are variably phosphorylated. The emerging studies suggest phosphorylation specific residues may alter the role tau. pTau can be explored through protein interactome studies. aim this study was to analyse phosphorylated at T217 (pT217), which biomarker one earliest accumulating AD. pT217 interactors were identified fresh-frozen human from 10 cases advanced AD using affinity purification-mass spectrometry. included balanced cohort APOE ε3/ε3 and ε4/ε4 genotypes ( n = 5 each) explore how apolipoprotein E altered interactions. results compared our previous dataset profiled PHF1-enriched determine if individual have different interactomes. 23 proteins as bona fide interactors, including known interactor SQSTM1. enriched fewer tau, suggesting an earlier stage pathology development. Notable five subunits CTLH E3 ubiquitin ligase (WDR26, ARMC8, GID8, RANBP9, MAEA), has not previously been linked In significantly interacted with 46 28 cases, but these overlapped. both genotypes. interactions SQSTM1, WDR26 RANBP9 validated co-immunoprecipitation immunofluorescent microscopy post-mortem tissue, showed colocalisation pathology. Our report for first time highlight significant novel

Language: Английский

Citations

0
Amyloid neuropathy, tauopathy, decreased cholinergic and dopaminergic neurons, long-term memory and motor deficits, and sleep disturbance in motopsin deficient mice DOI
Fumiaki Yokoi, Yusuke Tanaka, Akiko Sakai

et al.

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: May 23, 2025

Language: Английский

Citations

0
A consensus platform for antibody characterization DOI
Riham Ayoubi, Joël Ryan, Sara González Bolívar

et al.

Nature Protocols, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Language: Английский

Citations

3
A novel monoclonal antibody generated by immunization with granular tau oligomers binds to tau aggregates at 423-430 amino acid sequence DOI Creative Commons
Yoshiyuki Soeda,

Emi Hayashi,

Naoko Nakatani

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 26, 2024

Abstract Prior to the formation of amyloid fibrils, pathological hallmark in tau-related neurodegenerative disease, tau monomers aggregate into a diverse range oligomers. Granular oligomers, consisting approximately 40 protein molecules, are present prefrontal cortex patients at Braak stages I-II, preclinical Alzheimer’s disease (AD). Antibodies granular oligomers as antigens have not been reported. Therefore, we generated new rat monoclonal antibodies by immunization with Three from different hybridoma clones showed stronger immunoreactivity and fibrils compared monomeric tau. Of three antibodies, 2D6-2C6 3000-fold greater P301L-tau transgenic (rTg4510) mice than non-transgenic mice, while MC1 antibody, which detects conformations tau, 5.5-fold increase. These results suggest that recognizes aggregates more specifically MC1. In AD subjects, recognized neurofibrillary tangles pretangles, co-localized within AT8-positive cells containing phosphorylated aggregates. The epitope is 423–430 amino acid (AA) sequence C-terminal regions. Taken together, novel 2D6-2C6, binds AA sequence.

Language: Английский

Citations

2
Drosophila appear resistant to trans-synaptic tau propagation DOI Creative Commons
James H. Catterson, Edmond N Mouofo, Inés López De Toledo Soler

et al.

Brain Communications, Journal Year: 2024, Volume and Issue: 6(4)

Published: Jan. 1, 2024

Abstract Alzheimer’s disease is the most common cause of dementia in elderly, prompting extensive efforts to pinpoint novel therapeutic targets for effective intervention. Among hallmark features development neurofibrillary tangles comprised hyperphosphorylated tau protein, whose progressive spread throughout brain associated with neuronal death. Trans-synaptic propagation has been observed mouse models, and indirect evidence via synapses human disease. Halting a promising target disease; thus, scalable model system screen modifiers would be very useful field. To this end, we sought emulate trans-synaptic Drosophila melanogaster. Employing trans-Tango circuit mapping technique, investigated whether spreads between synaptically connected neurons. Immunohistochemistry confocal imaging were used look propagation. Examination hundreds flies expressing four different constructs two distinct populations reveals robust resistance tau. This persisted lines concurrent expression amyloid-β, global knock-in provide template downstream neurons, manipulations temperature. These negative data are important field as establish that subsets neurons unlikely perform screens find mechanisms reduce The inherent may serve valuable clue, offering insights into strategies impeding future studies.

Language: Английский

Citations

2
Ac Magnetic Field-Driven Wireless Charging Dual-Oriented Fibrous Magnetoelectric Scaffold Cfo/Pvdf Promotes Peripheral Nerve Repair DOI
Nan Li, Lu Wang, Pengrui Dang

et al.

Published: Jan. 1, 2024

Language: Английский

Citations

0
AC magnetic field-driven wireless charging dual-oriented fibrous magnetoelectric scaffold CFO/PVDF promotes peripheral nerve repair DOI
Lu Wang, Pengrui Dang,

Huimin Zheng

et al.

Colloids and Surfaces A Physicochemical and Engineering Aspects, Journal Year: 2024, Volume and Issue: 701, P. 134822 - 134822

Published: July 14, 2024

Language: Английский

Citations

0
Complex Regulation of Tau Phosphorylation by the Endothelin System in Brain Microvascular Endothelial Cells (BMVECs): Link to Barrier Function DOI Creative Commons
Eda Karakaya, Yasir Abdul, Jazlyn Edwards

et al.

Clinical Science, Journal Year: 2024, Volume and Issue: 138(21), P. 1329 - 1341

Published: Oct. 2, 2024

Endothelin-1 (ET-1), the most potent vasoconstrictor identified to date, contributes cerebrovascular dysfunction. ET-1 levels in postmortem brain specimens from individuals diagnosed with Alzheimer's disease (AD) and related dementias (ADRD) were shown be cerebral hypoxia severity. ET-1-mediated vascular dysfunction ensuing cognitive deficits have also been reported experimental models of AD ADRD. Moreover, studies showed that secreted microvascular endothelial cells (BMVECs) can affect neurovascular unit integrity an autocrine paracrine manner. Vascular contributions impairment dementia (VCID) is a leading ADRD cause known free neuronal tau pathology, hallmark AD. However, recent study cytotoxic hyperphosphorylated (p-tau) accumulation, which fails bind or stabilize microtubules BMVECs VCID. Thus, aimed determine impact on microtubule organization, barrier function BMVECs. Cells stimulated 1 μM for 24 h presence/absence ETA (BQ123; 20 μM) ETB (BQ788; receptor antagonists. Cell lysates assayed array phosphorylation site-specific antibodies organization/stabilization markers. stimulation increased p-tau Thr231 but decreased Ser199, Ser262, Ser396, Ser214 only presence antagonism. impaired These novel findings suggest (1) dysregulation may contribute (2) ET system early intervention target prevent tau-mediated disruption BMVEC function.

Language: Английский

Citations

0