Catechol-O-methyltransferase, Cognition and Alzheimer's Disease

Perković, Matea Nikolac; Štrac, Dubravka Švob; Tudor, Lucija; Konjevod, Marcela; Erjavec, Gordana Nedić; Pivac, Nela

doi:10.2174/1567205015666171212094229

Cited by 33 publications

(24 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also found that brain EV are significantly loaded with higher levels of essential brain enzymes during the preclinical stage of the disease, which included protein-L-isoaspartate (D-aspartate) omethyltransferase (PCMT1), neuroendocrine convertase 2 (PCSK2), dihydropyrimidinase-like 2 (DPYLS2), and biliverdin reductase-A (BLVRA). All these enzymes have previously been implicated in AD [60][61][62][63]. We also observed that the levels of these enzymes in brain EV, albeit upregulated in preclinical AD, were significantly downregulated throughout the entire disease progression.…”

Section: Discussionsupporting

confidence: 69%

Alzheimer’s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles

et al. 2020

View full text Add to dashboard Cite

Background: The contributions of brain intercellular communication mechanisms, specifically extracellular vesicles (EV), to the progression of Alzheimer's disease (AD) remain poorly understood. Methods: Here, we investigated the role(s) of brain EV in the progressive course of AD through unbiased proteome-wide analyses of temporal lobe-derived EV and proteome-label quantitation of complementary remaining brain portions. Furthermore, relevant proteins identified were further screened by multiple reaction monitoring. Results: Our data indicate that EV biogenesis was altered during preclinical AD with the genesis of a specific population of EV containing MHC class-type markers. The significant presence of the prion protein PrP was also manifested in these brain vesicles during preclinical AD. Similarly, sequestration of amyloid protein APP in brain EV coincided with the observed PrP patterns. In contrast, active incorporation of the mitophagy protein GABARAP in these brain vesicles was disrupted as AD progressed. Likewise, disrupted incorporation of LAMP1 in brain EV was evident from the initial manifestation of AD clinical symptoms, although the levels of the protein remained significantly upregulated in the temporal lobe of diseased brains. Conclusions: Our findings indicate that impaired autophagy in preclinical AD coincides with the appearance of proinflammatory and neuropathological features in brain extracellular vesicles, facts that moderately remain throughout the entire AD progression. Thus, these data highlight the significance of brain EV in the establishment of AD neuropathology and represent a further leap toward therapeutic interventions with these vesicles in human dementias.

show abstract

Section: Discussionsupporting

confidence: 69%

Alzheimer’s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Dopaminergic neurons are also closely associated with AD pathology, and several alterations in the dopaminergic system have been reported in AD patients (Burns et al, 2005;Rossato et al, 2009). Dopaminergic neurons in the prefrontal cortex participate in the formation of cognitive memory (Perkovic et al, 2018). Loss of dopaminergic neurons affects synaptic plasticity in hippocampal CA1 neurons in AD (Nobili et al, 2017).…”

Section: Selenok Selenot Selenos and Selenommentioning

confidence: 99%

Roles of Selenoproteins in Brain Function and the Potential Mechanism of Selenium in Alzheimer’s Disease

Zhang

Song

2021

Front. Neurosci.

View full text Add to dashboard Cite

Selenium (Se) and its compounds have been reported to have great potential in the prevention and treatment of Alzheimer’s disease (AD). However, little is known about the functional mechanism of Se in these processes, limiting its further clinical application. Se exerts its biological functions mainly through selenoproteins, which play vital roles in maintaining optimal brain function. Therefore, selenoproteins, especially brain function-associated selenoproteins, may be involved in the pathogenesis of AD. Here, we analyze the expression and distribution of 25 selenoproteins in the brain and summarize the relationships between selenoproteins and brain function by reviewing recent literature and information contained in relevant databases to identify selenoproteins (GPX4, SELENOP, SELENOK, SELENOT, GPX1, SELENOM, SELENOS, and SELENOW) that are highly expressed specifically in AD-related brain regions and closely associated with brain function. Finally, the potential functions of these selenoproteins in AD are discussed, for example, the function of GPX4 in ferroptosis and the effects of the endoplasmic reticulum (ER)-resident protein SELENOK on Ca2+ homeostasis and receptor-mediated synaptic functions. This review discusses selenoproteins that are closely associated with brain function and the relevant pathways of their involvement in AD pathology to provide new directions for research on the mechanism of Se in AD.

show abstract

“…2, COMT is known to influence synaptic plasticity and dopamine metabolism, both of which are associated with cognition. In this context, two point mutations (i.e., Val108Met and rs4680 -> Val158Met) in this gene were identified to be predictors of cognition scores in AD patients through independent studies [30,31]. Interestingly, the latter mutation along with rs4646312 in COMT has been associated with T2DM [32].…”

Section: Comorbidity In Ad and T2dm Explained By Mechanistic Bel Graphsmentioning

confidence: 99%

Data-Driven Modeling of Knowledge Assemblies in Understanding Comorbidity Between Type 2 Diabetes Mellitus and Alzheimer’s Disease

Karki

Madan

Gadiya

et al. 2020

JAD

View full text Add to dashboard Cite

Background: Recent studies have suggested comorbid association between Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) through identification of shared molecular mechanisms. However, the inference is pre-dominantly literature-based and lacks interpretation of pre-disposed genomic variants and transcriptomic measurables. Objective: In this study, we aim to identify shared genetic variants and dysregulated genes in AD and T2DM and explore their functional roles in the comorbidity between the diseases. Methods: The genetic variants for AD and T2DM were retrieved from GWAS catalog, GWAS central, dbSNP, and DisGeNet and subjected to linkage disequilibrium analysis. Next, shared variants were prioritized using RegulomeDB and Polyphen-2. Afterwards, a knowledge assembly embedding prioritized variants and their corresponding genes was created by mining relevant literature using Biological Expression Language. Finally, coherently perturbed genes from gene expression meta-analysis were mapped to the knowledge assembly to pinpoint biological entities and processes and depict a mechanistic link between AD and T2DM. Results: Our analysis identified four genes (i.e., ABCG1, COMT, MMP9, and SOD2) that could have dual roles in both AD and T2DM. Using cartoon representation, we have illustrated a set of causal events surrounding these genes which are associated to biological processes such as oxidative stress, insulin resistance, apoptosis and cognition. Conclusion: Our approach of using data as the driving force for unraveling disease etiologies eliminates literature bias and enables identification of novel entities that serve as the bridge between comorbid conditions.

show abstract

Catechol-O-methyltransferase, Cognition and Alzheimer's Disease

Abstract: Better understanding of the role of COMT in cognitive processes in AD, as well as integration of neurobiological, genetic, genomic and epigenetic data, might help in developing new potential therapies of cognitive impairments and psychotic symptoms, characteristic features of AD.

Cited by 33 publications

References 0 publications

Alzheimer’s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles

Alzheimer’s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles

Roles of Selenoproteins in Brain Function and the Potential Mechanism of Selenium in Alzheimer’s Disease

Data-Driven Modeling of Knowledge Assemblies in Understanding Comorbidity Between Type 2 Diabetes Mellitus and Alzheimer’s Disease

Contact Info

Product

Resources

About