The role of phenothiazine derivatives in autophagy regulation: A systematic review

Otręba, Michał; Stojko, Jerzy; Rzepecka‐Stojko, Anna

doi:10.1002/jat.4397

Cited by 10 publications

(4 citation statements)

References 48 publications

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“…Antipsychotics were recently shown to induce the processes of autophagy in the cells. In schizophrenia, autophagy processes are disrupted, and the authors believe that the induction of autophagy by some antipsychotics makes it possible to eliminate damaged brain cells from the areas associated with impaired thinking [36][37][38][39][40][41]. One can assume that such damaged brain cells belong to the fraction of cells with a high content of f-SatIII repeats, which cannot function normally and are eliminated.…”

Section: Discussionmentioning

confidence: 99%

Antipsychotics Affect Satellite III (1q12) Copy Number Variations in the Cultured Human Skin Fibroblasts

Ershova

Savinova

Kameneva

et al. 2023

IJMS

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The fragment of satellite III (f-SatIII) is located in pericentromeric heterochromatin of chromosome 1. Cell with an enlarged f-SatIII block does not respond to various stimuli and are highly stress-susceptible. The fraction of f-SatIII in the cells of schizophrenia patients changed during antipsychotic therapy. Therefore, antipsychotics might reduce the f-SatIII content in the cells. We studied the action of haloperidol, risperidone and olanzapine (3 h, 24 h, 96 h) on human skin fibroblast lines (n = 10). The f-SatIII contents in DNA were measured using nonradioactive quantitative hybridization. RNASATIII were quantified using RT-qPCR. The levels of DNA damage markers (8-oxodG, γ-H2AX) and proteins that regulate apoptosis and autophagy were determined by flow cytometry. The antipsychotics reduced the f-SatIII content in DNA and RNASATIII content in RNA from HSFs. After an exposure to the antipsychotics, the autophagy marker LC3 significantly increased, while the apoptosis markers decreased. The f-SatIII content in DNA positively correlated with RNASATIII content in RNA and with DNA oxidation marker 8-oxodG, while negatively correlated with LC3 content. The antipsychotics arrest the process of f-SatIII repeat augmentation in cultured skin fibroblasts via the transcription suppression and/or through upregulated elimination of cells with enlarged f-SatIII blocks with the help of autophagy.

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Section: Discussionmentioning

confidence: 99%

Antipsychotics Affect Satellite III (1q12) Copy Number Variations in the Cultured Human Skin Fibroblasts

Ershova

Savinova

Kameneva

et al. 2023

IJMS

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“…DFT/TD‐DFT studies were in agreement with the experimental observations. These NIR absorbing phenothiazine embedded porphyrinoids will have potential applications in material [23] and medical [24] fields.…”

Section: Discussionmentioning

confidence: 99%

Synthesis of Phenothiazine Embedded Heteroporphyrins

Tripathi,

Sinha,

Ravikanth

2023

Chemistry An Asian Journal

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A series of phenothiazine embedded heteroporphyrins containing one phenothiazine unit, two pyrrole rings and one heterocycle such as furan, thiophene, selenophene and tellurophene connected via four meso carbons were synthesized. The macrocycles were synthesized by condensing the phenothiazine based tripyrrane with corresponding 2,5‐bis(hydroxymethyl)heterocycle under BF3 ⋅ OEt2 catalyzed conditions and compared the structural, spectral, and electrochemical properties with the reported phenothiazinophyrins. The studies showed that the phenothiazine embedded heteroporphyrins were nonaromatic and electronic properties were significantly altered by replacing the pyrrole ring from phenothiazinophyrin with different heterocycles. The X‐ray structure of phenothiazine embedded thiaporphyrin revealed that the macrocycle was distorted with an inverted thiophene ring. Both mono‐protonated and diprotonated derivatives of macrocycles were generated by the controlled addition of trifluoroacetic acid to the macrocycles. The macrocyclic protons experienced upfield/downfield shifts in protonated derivatives compared to their corresponding neutral phenothiazine embedded heteroporphyrins. However, the heterocyclic ring in both mono‐ and diprotonated derivatives retained its inverted conformation. The macrocycles in their neutral and protonated form exhibit nonaromatic absorption features. The studies indicated the electron rich nature of macrocycles and DFT/TD‐DFT studies were carried out to justify the experimental observations.

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“…Antipsychotics such as phenothiazines have been noted to regulate autophagy, contributing to their therapeutic effects in SCZ patients [ 20 ]. A recent meta-analysis highlighted that phenothiazine-like antipsychotics, including chlorpromazine, fluphenazine, methotrimeprazine, perphenazine, prochlorperazine, promethazine, thioridazine, and trifluoperazine, can modulate autophagy [ 21 ]. Overall, the role of autophagy in SCZ is multifaceted, encompassing neuronal homeostasis, disease pathophysiology, and symptom modulation, with its regulation being mediated through specific genes and pathways, underscoring the complexity and significance of this process in SCZ.…”

Section: Introductionmentioning

confidence: 99%

Autophagy-related gene model as a novel risk factor for schizophrenia

Tan,

Zhu,

Hashimoto

2024

Transl Psychiatry

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Autophagy, a cellular process where cells degrade and recycle their own components, has garnered attention for its potential role in psychiatric disorders, including schizophrenia (SCZ). This study aimed to construct and validate a new autophagy-related gene (ARG) risk model for SCZ. First, we analyzed differential expressions in the GSE38484 training set, identifying 4,754 differentially expressed genes (DEGs) between SCZ and control groups. Using the Human Autophagy Database (HADb) database, we cataloged 232 ARGs and pinpointed 80 autophagy-related DEGs (AR-DEGs) after intersecting them with DEGs. Subsequent analyses, including metascape gene annotation, pathway and process enrichment, and protein-protein interaction enrichment, were performed on the 80 AR-DEGs to delve deeper into their biological roles and associated molecular pathways. From this, we identified 34 candidate risk AR-DEGs (RAR-DEGs) and honed this list to final RAR-DEGs via a constructed and optimized logistic regression model. These genes include VAMP7, PTEN, WIPI2, PARP1, DNAJB9, SH3GLB1, ATF4, EIF4G1, EGFR, CDKN1A, CFLAR, FAS, BCL2L1 and BNIP3. Using these findings, we crafted a nomogram to predict SCZ risk for individual samples. In summary, our study offers deeper insights into SCZ’s molecular pathogenesis and paves the way for innovative approaches in risk prediction, gene-targeted diagnosis, and community-based SCZ treatments.

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The role of phenothiazine derivatives in autophagy regulation: A systematic review

Cited by 10 publications

References 48 publications

Antipsychotics Affect Satellite III (1q12) Copy Number Variations in the Cultured Human Skin Fibroblasts

Antipsychotics Affect Satellite III (1q12) Copy Number Variations in the Cultured Human Skin Fibroblasts

Synthesis of Phenothiazine Embedded Heteroporphyrins

Autophagy-related gene model as a novel risk factor for schizophrenia

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