Comparing in vitro protein aggregation modelling using strategies relevant to neuropathologies DOI Creative Commons
André Nadais, Diogo Trigo, Ana Gabriela Henriques

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Abstract Although protein aggregation is involved in physiological ageing-related processes, it also remarkably associated with several neuropathologies, including Alzheimer´s (AD) and Parkinson´s disease (PD). The first characterized by hyperphosphorylated tau Aβ peptide deposition, thus forming intracellular neurofibrillary tangles extracellular senile plaques, respectively; while, PD, α-synuclein aggregates deposits as Lewy bodies. Considerable research has focused on developing models to be explored tools. In the present work, four alternative for studying were compared, namely treatment with: toxic peptide, isoflavone rotenone, ATP synthase inhibitor oligomycin, proteosome MG-132. All treatments result aggregation-relevant events a human neuronal cell line, but significant model-dependent differences observed. terms of promoting aggregate formation, MG-132 provoked greatest effect, only was an increase HSP-70 chaperone. fact, type formed appear dependent employed, supports hypothesis that exposure relevant AD model, rotenone fact good model PD. Furthermore, results revealed phosphorylation formation expected, co-localized induction model. summary, different molecular processes can induced using distinct modelling strategies, these used study protein-aggregation related neuropathologies.

Language: Английский

Volume electron microscopy reveals human retinal mitochondria that align with reflective bands in optical coherence tomography [Invited] DOI Creative Commons
Deepayan Kar, Yeon Jin Kim, Orin Packer

et al.

Biomedical Optics Express, Journal Year: 2023, Volume and Issue: 14(10), P. 5512 - 5512

Published: Aug. 25, 2023

Mitochondria are candidate reflectivity signal sources in optical coherence tomography (OCT) retinal imaging. Here, we use deep-learning-assisted volume electron microscopy of human retina and vivo imaging to map mitochondria networks the outer plexiform layer (OPL), where photoreceptors synapse with second-order interneurons. We observed alternating layers high low mitochondrial abundance anatomical OPL adjacent inner nuclear (INL). Subcellular resolution OCT eyes revealed multiple reflective bands that matched corresponding INL combined sublayers. Data linking specific defined may help improve clinical diagnosis evaluation mitochondria-targeting therapies.

Language: Английский

Citations

6
Analyses of single-cell and bulk RNA sequencing combined with machine learning reveal the expression patterns of disrupted mitophagy in schizophrenia DOI Creative Commons

Wei Yang,

Kun Lian, Jing Ye

et al.

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 17, 2024

Background Mitochondrial dysfunction is an important factor in the pathogenesis of schizophrenia. However, relationship between mitophagy and schizophrenia remains to be elucidated. Methods Single-cell RNA sequencing datasets peripheral blood brain organoids from SCZ patients healthy controls were retrieved. Mitophagy-related genes that differentially expressed two groups screened. The diagnostic model based on key was constructed using machine learning methods, immune cells analyzed. data used calculate score (Mitoscore). Results We found 7 construct a model. related infiltration neutrophils, activated dendritic cells, resting NK regulatory T memory CD8 cells. In addition, we identified 12 cell clusters Mitoscore, most abundant neurons further divided into three subgroups. at single-cell level showed Mitohigh_Neuron established novel interaction with endothelial via SPP1 signaling pathway, suggesting their distinct roles pathogenesis. Conclusion signature for provides new insights disease possibilities its diagnosis treatment.

Language: Английский

Citations

1
A role of altered inflammation-related gene expression in cerebral small vessel disease with cognitive impairment DOI
Л А Добрынина, Angelina G. Makarova, А. А. Шабалина

et al.

S S Korsakov Journal of Neurology and Psychiatry, Journal Year: 2023, Volume and Issue: 123(9), P. 58 - 58

Published: Jan. 1, 2023

To identify the role of changes in expression inflammation-related genes cerebral microangiopathy/cerebral small vessel disease (cSVD).Forty-four cSVD patients (mean age 61.4±9.2) and 11 controls 57.3±9.7) were studied. Gene was assessed on an individual NanoString nCounter panel 58 4 reference genes. A set generated based converging results complete genome-wide association studies (GWAS) Alzheimer's (AD) circulating markers associated with vascular wall Brain lesions cSVD. RNA isolated from blood leukocytes analyzed Analysis System, followed by analysis nSolver 4.0. Results verified real-time PCR.CSVD had a significant decrease BIN1 (log2FC=-1.272; p=0.039) VEGFA (log2FC=-1.441; p=0.038) compared to controls, which showed predictive ability for The cut-off 5.76 a.u. (sensitivity 73%; specificity 75%) 9.27 64%; 86%). Reduced (p=0.011), VEGFC (p=0.017), CD2AP (p=0.044) cognitive impairment (CI). There direct correlation between scores Montreal Cognitive Assessment test delayed memory.The possible prediction reduced levels BIN1, clinically CI indicate their importance development progression disease. established these pathogenesis AD suggests that similar profile may be one conditions comorbidity two pathologies.Уточнить роль изменения экспрессии генов, ассоциированных с воспалением, при церебральной микроангиопатии (ЦМА).Обследованы 44 пациента ЦМА (средний возраст 61,4±9,2 года) и добровольцев 57,3±9,7 года). Экспрессия генов оценивалась на индивидуальной панели из эталонных генов. Набор сформирован основе конвергирующих результатов полногеномных исследований ассоциаций болезни Альцгеймера циркулирующих маркеров, поражением сосудистой стенки мозга ЦМА. РНК выделяли лейкоцитов крови анализировали помощью последующий анализ проводили в Результаты проверяли методом ПЦР режиме реального времени.Пациенты по сравнению контролем имели значимое снижение (log2FC=–1,272; p=0,039) (log2FC=–1,441; p=0,038), которые показали предиктивную способность отношении Пороговое значение 5,76 у.е. (чувствительность 73%, специфичность 75%), 9,27 64%, Снижение (p=0,011), (p=0,017), (p=0,044) было связано клинически выраженными когнитивными расстройствами. Выявлена значимая прямая корреляционная связь результата тестирования Монреальской шкале оценки когнитивных функций экспрессией VEGFC; теста отсроченного запоминания — VEGFC.Возможность предикции развития сниженному уровню значимых расстройств со снижением указывают их развитии прогрессировании заболевания. Установленная значимость данных патогенезе указывает то, что сходные профиля могут быть одним условий коморбидности двух патологий.

Language: Русский

Citations

1
The Role of Changes in the Expression of Inflammation-Associated Genes in Cerebral Small Vessel Disease with Cognitive Impairments DOI
Л А Добрынина,

A. G. Makarova,

А.А. Шабалина

et al.

Neuroscience and Behavioral Physiology, Journal Year: 2024, Volume and Issue: 54(2), P. 210 - 221

Published: Feb. 1, 2024

Language: Английский

Citations

0
Comparing in vitro protein aggregation modelling using strategies relevant to neuropathologies DOI Creative Commons
André Nadais, Diogo Trigo, Ana Gabriela Henriques

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Abstract Although protein aggregation is involved in physiological ageing-related processes, it also remarkably associated with several neuropathologies, including Alzheimer´s (AD) and Parkinson´s disease (PD). The first characterized by hyperphosphorylated tau Aβ peptide deposition, thus forming intracellular neurofibrillary tangles extracellular senile plaques, respectively; while, PD, α-synuclein aggregates deposits as Lewy bodies. Considerable research has focused on developing models to be explored tools. In the present work, four alternative for studying were compared, namely treatment with: toxic peptide, isoflavone rotenone, ATP synthase inhibitor oligomycin, proteosome MG-132. All treatments result aggregation-relevant events a human neuronal cell line, but significant model-dependent differences observed. terms of promoting aggregate formation, MG-132 provoked greatest effect, only was an increase HSP-70 chaperone. fact, type formed appear dependent employed, supports hypothesis that exposure relevant AD model, rotenone fact good model PD. Furthermore, results revealed phosphorylation formation expected, co-localized induction model. summary, different molecular processes can induced using distinct modelling strategies, these used study protein-aggregation related neuropathologies.

Language: Английский

Citations

0