TDP-43 as a potential retinal biomarker for neurodegenerative diseases DOI Creative Commons
Margit Glashutter, Printha Wijesinghe, Joanne A. Matsubara

и другие.

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Фев. 12, 2025

TDP-43 proteinopathies are a spectrum of neurodegenerative diseases (NDDs) characterized by the pathological cytoplasmic aggregation protein. These include amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer’s disease (AD), chronic traumatic encephalopathy (CTE), and others. in eye shows promise as biomarker for these NDDs. Several studies have identified inclusions retinal layers donors with ALS, FTLD, AD, CTE, other conditions using immunohistochemistry. Our findings suggest that aggregates human retina most prevalent FTLD-TDP, suggesting may provide reliable context studying potential biomarker. Animal model been pivotal exploring TDP-43’s roles retina, including its nuclear localization, RNA binding properties, interactions proteins. Despite advances, more research is needed to develop therapeutic strategies. A major limitation autopsy lack corresponding brain pathology assessments confirm proteinopathy diagnosis staging. Other limitations small sample sizes, antemortem clinical histories, limited comparisons across multiple Future directions NDDs tracers, hyperspectral imaging, oculomics, machine learning development.

Язык: Английский

TDP-43 Pathology in Alzheimer’s Disease DOI Creative Commons
Axel Meneses, Shunsuke Koga, Justin O’Leary

и другие.

Molecular Neurodegeneration, Год журнала: 2021, Номер 16(1)

Опубликована: Дек. 20, 2021

Abstract Transactive response DNA binding protein of 43 kDa (TDP-43) is an intranuclear encoded by the TARDBP gene that involved in RNA splicing, trafficking, stabilization, and thus, regulation expression. Cytoplasmic inclusion bodies containing phosphorylated truncated forms TDP-43 are hallmarks amyotrophic lateral sclerosis (ALS) a subset frontotemporal lobar degeneration (FTLD). Additionally, inclusions have been found up to 57% Alzheimer’s disease (AD) cases, most often limbic distribution, with or without hippocampal sclerosis. In some deposits also neurons neurofibrillary tangles. AD patients pathology increased severity cognitive impairment compared those pathology. Furthermore, common genetic risk factor for AD, apolipoprotein E4 ( APOE4 ), associated frequency These findings provide strong evidence integral part multiple neurodegenerative conditions, including AD. Here, we review biology pathobiology focus on its role We emphasize need studies mechanisms lead pathology, especially setting age-related disorders such as

Язык: Английский

Процитировано

179
Frontotemporal Dementia, Where Do We Stand? A Narrative Review DOI Open Access
Annibale Antonioni,

Emanuela Maria Raho,

Piervito Lopriore

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(14), С. 11732 - 11732

Опубликована: Июль 21, 2023

Frontotemporal dementia (FTD) is a neurodegenerative disease of growing interest, since it accounts for up to 10% middle-age-onset dementias and entails social, economic, emotional burden the patients caregivers. It characterised by (at least initially) selective degeneration frontal and/or temporal lobe, generally leading behavioural alterations, speech disorders, psychiatric symptoms. Despite recent advances, given its extreme heterogeneity, an overview that can bring together all data currently available still lacking. Here, we aim provide state art on pathogenesis this disease, starting with established findings integrating them more ones. In particular, advances in genetics field will be examined, assessing relation both clinical manifestations histopathological findings, as well considering link other diseases, such amyotrophic lateral sclerosis (ALS). Furthermore, current diagnostic criteria explored, including neuroimaging methods, nuclear medicine investigations, biomarkers biological fluids. Of note, promising information provided neurophysiological i.e., electroencephalography non-invasive brain stimulation techniques, concerning alterations networks neurotransmitter systems reviewed. Finally, experimental therapies considered.

Язык: Английский

Процитировано

48
Neurodegenerative disorders: Mechanisms of degeneration and therapeutic approaches with their clinical relevance DOI Creative Commons
Dnyandev Gadhave, Vrashabh V. Sugandhi, Saurav Kumar Jha

и другие.

Ageing Research Reviews, Год журнала: 2024, Номер 99, С. 102357 - 102357

Опубликована: Июнь 1, 2024

Neurodegenerative disorders (NDs) are expected to pose a significant challenge for both medicine and public health in the upcoming years due global demographic changes. NDs mainly represented by degeneration/loss of neurons, which is primarily accountable severe mental illness. This neuronal degeneration leads many neuropsychiatric problems permanent disability an individual. Moreover, tight junction brain, blood-brain barrier (BBB)has protective feature, functioning as biological that can prevent medicines, toxins, foreign substances from entering brain. However, delivering any medicinal agent brain (i.e., Multiple sclerosis, Alzheimer's, Parkinson's, etc.) enormously challenging. There approved therapies address NDs, but most them only help treat associated manifestations. The available have failed control progression certain factors, i.e., BBB drug-associated undesirable effects. extremely complex pathology, with pathogenic mechanisms involved initiation progression; thereby, limited survival rate has been observed ND patients. Hence, understanding exact mechanism behind crucial developing alternative approaches improving patients' rates. Thus, present review sheds light on different cellular novel therapeutic their clinical relevance, will assist researchers alternate strategies limitations conventional therapies. current work offers scope into near future improve approach NDs.

Язык: Английский

Процитировано

28
Cellular and molecular mechanisms of the blood–brain barrier dysfunction in neurodegenerative diseases DOI Creative Commons

Tongli Chen,

Yan Dai,

Chenghao Hu

и другие.

Fluids and Barriers of the CNS, Год журнала: 2024, Номер 21(1)

Опубликована: Июль 19, 2024

Abstract Background Maintaining the structural and functional integrity of blood–brain barrier (BBB) is vital for neuronal equilibrium optimal brain function. Disruptions to BBB performance are implicated in pathology neurodegenerative diseases. Main body Early indicators multiple disorders humans animal models include impaired stability, regional cerebral blood flow shortfalls, vascular inflammation associated with dysfunction. Understanding cellular molecular mechanisms dysfunction crucial elucidating sustenance neural computations under pathological conditions developing treatments these This paper initially explores definition BBB, along signaling pathways regulating flow, inflammation. Subsequently, we review current insights into dynamics Alzheimer’s disease, Parkinson's amyotrophic lateral sclerosis, sclerosis. The concludes by proposing a unified mechanism whereby contributes disorders, highlights potential BBB-focused therapeutic strategies targets, outlines lessons learned future research directions. Conclusions breakdown significantly impacts development progression diseases, unraveling underlying elucidate how sustained devise approaches.

Язык: Английский

Процитировано

23
Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus DOI Creative Commons
Hong Zhang, Huazhang Guo, Danni Li

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 6, 2024

Abstract TDP-43 is implicated in the dynamic formation of nuclear bodies and stress granules through phase separation. In diseased states, it can further condense into pathological aggregates nucleus cytoplasm, contributing to onset amyotrophic lateral sclerosis. this study, we evaluate effect graphene quantum dots (GQDs) with different functional groups on TDP-43’s separation aggregation various cellular locations. We find that halogen atom-doped GQDs (GQDs-Cl, Cl-GQDs-OH) penetrate envelope, inhibiting assembly under oxidative or hyperosmotic environments, reduce amyloid disease-associated phosphorylation TDP-43. Mechanistic analysis reveals GQDs-Cl Cl-GQDs-OH modulate hydrophobic electrostatic interactions. Our findings highlight potential modulating protein condensation aggregation, offering direction for innovative design aggregation.

Язык: Английский

Процитировано

22
AI-based differential diagnosis of dementia etiologies on multimodal data DOI Creative Commons

Chonghua Xue,

Sahana S. Kowshik,

Diala Lteif

и другие.

Nature Medicine, Год журнала: 2024, Номер 30(10), С. 2977 - 2989

Опубликована: Июль 4, 2024

Abstract Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an artificial intelligence (AI) model that harnesses broad array data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations multimodal neuroimaging, identify the etiologies contributing individuals. The study, drawing on 51,269 participants 9 independent, geographically diverse datasets, facilitated identification 10 distinct etiologies. It aligns diagnoses with similar strategies, ensuring robust predictions even incomplete data. Our achieved microaveraged area under receiver operating characteristic curve (AUROC) 0.94 classifying individuals normal cognition, mild cognitive impairment dementia. Also, AUROC was 0.96 differentiating demonstrated proficiency addressing mixed cases, mean 0.78 two co-occurring pathologies. In randomly selected subset 100 neurologist assessments augmented by our AI exceeded neurologist-only 26.25%. Furthermore, aligned biomarker evidence its associations different proteinopathies were substantiated through postmortem findings. framework has potential be integrated as screening tool clinical settings drug trials. Further prospective studies are needed confirm ability improve patient care.

Язык: Английский

Процитировано

21
Polystyrene nanoparticles trigger aberrant condensation of TDP-43 and amyotrophic lateral sclerosis-like symptoms DOI
Hang Sun, Bingwei Yang, Qiong Li

и другие.

Nature Nanotechnology, Год журнала: 2024, Номер 19(9), С. 1354 - 1365

Опубликована: Июнь 7, 2024

Язык: Английский

Процитировано

19
RNA dysregulation in neurodegenerative diseases DOI Creative Commons
Yini Li, Shuying Sun

The EMBO Journal, Год журнала: 2025, Номер 44(3), С. 613 - 638

Опубликована: Янв. 9, 2025

Dysregulation of RNA processing has in recent years emerged as a significant contributor to neurodegeneration. The diverse mechanisms and molecular functions underlying underscore the essential role regulation maintaining neuronal health function. molecules are bound by RNA-binding proteins (RBPs), interactions between RNAs RBPs commonly affected In this review, we highlight progress understanding dysregulated RNA-processing pathways causes RBP dysfunction across various neurodegenerative diseases. We discuss both established emerging RNA-mediated neuropathogenesis rapidly evolving field. Furthermore, explore development potential RNA-targeting therapeutic approaches for treatment

Язык: Английский

Процитировано

3
TDP-43 pathology: From noxious assembly to therapeutic removal DOI
Sean S. Keating, Rebecca San Gil, Molly E. V. Swanson

и другие.

Progress in Neurobiology, Год журнала: 2022, Номер 211, С. 102229 - 102229

Опубликована: Янв. 29, 2022

Язык: Английский

Процитировано

52
The Role of TDP-43 in Neurodegenerative Disease DOI

Yan-Zhe Liao,

Jing Ma,

Jie-Zhi Dou

и другие.

Molecular Neurobiology, Год журнала: 2022, Номер 59(7), С. 4223 - 4241

Опубликована: Май 2, 2022

Язык: Английский

Процитировано

52