Assessment of tau phosphorylation and β‐amyloid pathology in human drug‐resistant epilepsy

Aroor, Alisha; Nguyen, Phuoc; Li, Yibo; Das, Rohit R.; Lugo, Joaquín N.; Brewster, Amy L.

doi:10.1002/epi4.12744

Cited by 5 publications

(2 citation statements)

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“…Aβ protein levels and their relationship with cognitive function have been investigated in patients with refractory epilepsy by analyzing cortical biopsies from the temporal lobes. The results revealed a strong compelling of Aβ deposits in the biopsied tissues, supporting the existence of Aβ deposits in patients with refractory epilepsy ( 39 ). In patients with refractory seizures, increased Aβ precursor protein was detected in temporal lobe or hippocampal sections ( 41 ).…”

Section: Discussionsupporting

confidence: 70%

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Protein profiling and assessment of amyloid beta levels in plasma in canine refractory epilepsy

Phochantachinda,

Chantong,

Reamtong

et al. 2023

Front. Vet. Sci.

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IntroductionThe relationship between epilepsy and cognitive dysfunction has been investigated in canines, and memory impairment was prevalent in dogs with epilepsy. Additionally, canines with epilepsy have greater amyloid-β (Aβ) accumulation and neuronal degeneration than healthy controls. The present study investigated plasma Aβ42 levels and performed proteomic profiling in dogs with refractory epilepsy and healthy dogs.MethodsIn total, eight dogs, including four healthy dogs and four dogs with epilepsy, were included in the study. Blood samples were collected to analyze Aβ42 levels and perform proteomic profiling. Changes in the plasma proteomic profiles of dogs were determined by nano liquid chromatography tandem mass spectrometry.Results and discussionThe plasma Aβ42 level was significantly higher in dogs with epilepsy (99 pg/mL) than in healthy dogs (5.9 pg/mL). In total, 155 proteins were identified, and of these, the expression of 40 proteins was altered in epilepsy. Among these proteins, which are linked to neurodegenerative diseases, 10 (25%) were downregulated in dogs with epilepsy, whereas 12 (30%) were upregulated. The expression of the acute phase proteins haptoglobin and α2-macroglobulin significantly differed between the groups. Complement factor H and ceruloplasmin were only detected in epilepsy dogs, suggesting that neuroinflammation plays a role in epileptic seizures. Gelsolin, which is involved in cellular processes and cytoskeletal organization, was only detected in healthy dogs. Gene Ontology annotation revealed that epilepsy can potentially interfere with biological processes, including cellular processes, localization, and responses to stimuli. Seizures compromised key molecular functions, including catalytic activity, molecular function regulation, and binding. Defense/immunity proteins were most significantly modified during the development of epilepsy. In Kyoto Encyclopedia of Genes and Genomes pathway analysis, complement and coagulation cascades were the most relevant signaling pathways affected by seizures. The findings suggested that haptoglobin, ceruloplasmin, α2-macroglobulin, complement factor H, and gelsolin play roles in canine epilepsy and Aβ levels based on proteomic profiling. These proteins could represent diagnostic biomarkers that, after clinical validation, could be used in veterinary practice as well as proteins relevant to disease response pathways. To determine the precise mechanisms underlying these relationships and their implications in canine epilepsy, additional research is required.

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Section: Discussionsupporting

confidence: 70%

“…Canine refractory epilepsy have a higher risk of developing CDS at a younger age than normal dogs ( 12 ). Multiple studies in animals and humans have revealed an association between Aβ and epilepsy ( 37 – 39 ). In our study, we first demonstrated significantly higher plasma Aβ levels in dogs with refractory epilepsy.…”

Section: Discussionmentioning

confidence: 99%

Protein profiling and assessment of amyloid beta levels in plasma in canine refractory epilepsy

Phochantachinda,

Chantong,

Reamtong

et al. 2023

Front. Vet. Sci.

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Assessment of tau phosphorylation and β‐amyloid pathology in human drug‐resistant epilepsy

Aroor

Nguyen

et al. 2023

Epilepsia Open

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Objective Epilepsy can be comorbid with cognitive impairments. Recent evidence suggests the possibility that cognitive decline in epilepsy may be associated with mechanisms typical of Alzheimer's disease (AD). Neuropathological hallmarks of AD have been found in brain biopsies surgically resected from patients with drug‐resistant epilepsies. These include hyperphosphorylation of the tau protein (p‐tau) that aggregates into neuropil threads (NT) or neurofibrillary tangles (NFT), as well as the presence of β‐amyloid (Aβ) deposits. While recent studies agree on these AD neuropathological findings in epilepsy, some contrast in their correlation to cognitive decline. Thus, to further address this question we determined the abundance of p‐tau and Aβ proteins along with their association with cognitive function in 12 cases of refractory epilepsy. Methods Cortical biopsies surgically extracted from the temporal lobes of patients with refractory epilepsy were processed for immunohistology and enzyme‐linked immunoassays to assess distribution and levels, respectively, of p‐tau (Antibodies: Ser202/Thr205; Thr205; Thr181) and Aβ proteins. In parallel, we measured the activation of mechanistic target of rapamycin (mTOR) via p‐S6 (Antibodies: Ser240/244; Ser235/236). Pearson correlation coefficient analysis determined associations between these proteins and neurophysiological scores for full‐scale intelligence quotient (FSIQ). Results We found a robust presence of p‐tau (Ser202/Thr205)‐related NT and NFT pathology, as well as Aβ deposits, and p‐S6 (Ser240/244; Ser235/236) in the epilepsy biopsies. We found no significant correlations between p‐tau (Thr205; Thr181), Aβ, or mTOR markers with FSIQ scores, although some correlation coefficients were modest to strong. Significance These findings strongly support the existence of hyperphosphorylated tau protein and Aβ deposits in patients with human refractory epilepsy. However, their relation to cognitive decline is still unclear and requires further investigation.

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Untargeted metabolomics‐based identification of bioactive compounds from Mangifera indica L. seed extracts in drug discovery through molecular docking and assessment of their anticancer potential

Kaneria,

Rakholiya,

Bavaliya

et al. 2024

J Sci Food Agric

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BackgroundMangifera indica L. (mango), a medicinal plant rich in biologically active compounds have potential to be used in disease‐preventing and health‐promoting products. The present investigation reveals and uncovers bioactive metabolites with remarkable therapeutic efficiency from mango (Family: Anacardiaceae) seeds.ResultsBiological activity was determined by antimicrobial, antioxidant, and anticancer assays, and metabolite profiling was performed on the gas chromatography coupled to quadrupole time‐of‐flight mass spectrometry (GC‐QTOF‐MS) and liquid chromatography coupled to quadrupole time‐of‐flight mass spectrometry (LC‐QTOF‐MS) platforms. Validation of active metabolites was carried out by in silico molecular docking (Molinspiration Cheminformatics Server and PASS). Extracted and identified metabolites were screened; 54 compounds associated with various groups were selected for the in silico interaction study.ConclusionsMolecular docking revealed lead molecules with a potential binding energy score, its efficacy and stable modulation with a selected protein domain. Investigation, directed by in vitro and in silico analysis, confirms mango seeds as an excellent source of potential metabolites as a therapeutic agent.This article is protected by copyright. All rights reserved.

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Assessment of tau phosphorylation and β‐amyloid pathology in human drug‐resistant epilepsy

Cited by 5 publications

References 58 publications

Protein profiling and assessment of amyloid beta levels in plasma in canine refractory epilepsy

Protein profiling and assessment of amyloid beta levels in plasma in canine refractory epilepsy

Assessment of tau phosphorylation and β‐amyloid pathology in human drug‐resistant epilepsy

Untargeted metabolomics‐based identification of bioactive compounds from Mangifera indica L. seed extracts in drug discovery through molecular docking and assessment of their anticancer potential

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