Cytochrome P450 isoforms in the brain encode cell specific hy perpolarizing factors with a common mechanism of action

Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.

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Decision-related feedback in visual cortex lacks spatial selectivity

Nature Communications ◽

10.1038/s41467-021-24629-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Katrina R. Quinn ◽

Lenka Seillier ◽

Daniel A. Butts ◽

Hendrikje Nienborg

Keyword(s):

Contextual Information ◽

Relevant Information ◽

Common Mechanism ◽

Spatial Selectivity ◽

Population Responses ◽

Stimulus Choice ◽

Visual Areas ◽

Computational Work ◽

Feature Based ◽

The Brain

AbstractFeedback in the brain is thought to convey contextual information that underlies our flexibility to perform different tasks. Empirical and computational work on the visual system suggests this is achieved by targeting task-relevant neuronal subpopulations. We combine two tasks, each resulting in selective modulation by feedback, to test whether the feedback reflected the combination of both selectivities. We used visual feature-discrimination specified at one of two possible locations and uncoupled the decision formation from motor plans to report it, while recording in macaque mid-level visual areas. Here we show that although the behavior is spatially selective, using only task-relevant information, modulation by decision-related feedback is spatially unselective. Population responses reveal similar stimulus-choice alignments irrespective of stimulus relevance. The results suggest a common mechanism across tasks, independent of the spatial selectivity these tasks demand. This may reflect biological constraints and facilitate generalization across tasks. Our findings also support a previously hypothesized link between feature-based attention and decision-related activity.

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Small Blood Vessel Disease in the Brain Theme Issue Overlapping protein accumulation profiles of CADASIL and CAA: Is there a common mechanism driving cerebral small vessel disease?

American Journal Of Pathology ◽

10.1016/j.ajpath.2020.11.015 ◽

2020 ◽

Author(s):

Kelly Z. Young ◽

Gang Xu ◽

Simon G. Keep ◽

Jimo Borjigin ◽

Michael M. Wang

Keyword(s):

Blood Vessel ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Common Mechanism ◽

Protein Accumulation ◽

Theme Issue ◽

Small Blood Vessel ◽

Vessel Disease ◽

The Brain

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In Silico Prediction of Drug–Drug Interactions Mediated by Cytochrome P450 Isoforms

Pharmaceutics ◽

10.3390/pharmaceutics13040538 ◽

2021 ◽

Vol 13 (4) ◽

pp. 538

Author(s):

Alexander V. Dmitriev ◽

Anastassia V. Rudik ◽

Dmitry A. Karasev ◽

Pavel V. Pogodin ◽

Alexey A. Lagunin ◽

...

Keyword(s):

Cytochrome P450 ◽

Drug Interactions ◽

Cytochromes P450 ◽

Investigational Drug ◽

Web Resource ◽

Average Accuracy ◽

Structural Formulas ◽

Cytochrome P450 Isoforms ◽

Leave One Out ◽

Important Drug

Drug–drug interactions (DDIs) can cause drug toxicities, reduced pharmacological effects, and adverse drug reactions. Studies aiming to determine the possible DDIs for an investigational drug are part of the drug discovery and development process and include an assessment of the DDIs potential mediated by inhibition or induction of the most important drug-metabolizing cytochrome P450 isoforms. Our study was dedicated to creating a computer model for prediction of the DDIs mediated by the seven most important P450 cytochromes: CYP1A2, CYP2B6, CYP2C19, CYP2C8, CYP2C9, CYP2D6, and CYP3A4. For the creation of structure–activity relationship (SAR) models that predict metabolism-mediated DDIs for pairs of molecules, we applied the Prediction of Activity Spectra for Substances (PASS) software and Pairs of Substances Multilevel Neighborhoods of Atoms (PoSMNA) descriptors calculated based on structural formulas. About 2500 records on DDIs mediated by these cytochromes were used as a training set. Prediction can be carried out both for known drugs and for new, not-yet-synthesized substances. The average accuracy of the prediction of DDIs mediated by various isoforms of cytochrome P450 estimated by leave-one-out cross-validation (LOO CV) procedures was about 0.92. The SAR models created are publicly available as a web resource and provide predictions of DDIs mediated by the most important cytochromes P450.

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