BioFactors最新文献

{"title":"Combinatorial effect of Apigenin-resveratrol on white adipocyte plasticity and trans-differentiation for activating lipid metabolism.","authors":"Sreelekshmi Sreekumar, Manikantan Syamala Kiran","doi":"10.1002/biof.2111","DOIUrl":"https://doi.org/10.1002/biof.2111","url":null,"abstract":"<p><p>Inducing browning in white adipocytes has emerged as a promising therapeutic approach for addressing obesity. Bioactive that modulate the WAT microenvironment to induce trans browning in white adipocytes have been explored as a strategy to control unregulated lipid storage. However, relying on a single bioactive for modulating lipid metabolism has proven insufficient in obese individuals during human trials, because these compounds primarily activate a single biochemical pathway in promoting browning. Consequently, there is a growing emphasis on targeting multiple pathways to ensure a safe and effective browning process. The present study investigated the combinatorial effect of bioactives namely Apigenin and Resveratrol for activating multiple pathways for effective trans-browning of white adipocytes. The combination was seen to promote the browning more effectively than the single bioactive, as the combination simultaneously activated multiple signaling pathways to induce angiogenesis-mediated browning in primary white adipocytes isolated from obese mice. Activation of PI3K signaling via estrogen receptor-α-dependent pathway resulted in simultaneous activation of angiogenesis and trans browning in white adipocytes. The study provides valuable insights into the potential use of bioactives in combination with therapeutic intervention to improve the overall health of obese subjects by enhancing lipid metabolism by activating trans-differentiation of white adipocytes.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morin overcomes doxorubicin resistance in human breast cancer by inducing DNA damage and modulating the LKB1/AMPK/mTORC1 signaling pathway.","authors":"Sushma Maharjan, Min-Gu Lee, Kyu-Shik Lee, Kyung-Soo Nam","doi":"10.1002/biof.2112","DOIUrl":"https://doi.org/10.1002/biof.2112","url":null,"abstract":"<p><p>Breast cancer chemoresistance hampers chemotherapy efficacy; researchers investigate the pharmacological activities of natural products for potential solutions. This study aimed to determine the effect of morin, a bioflavonoid isolated from Maclura pomifera, on two Dox-resistant human breast cancer cell lines MDA-MB-231 (MDA-DR) and MCF-7 (MCF-DR). Sulforhodamine B and colony-forming assays demonstrated the cytotoxic effect of morin on both cell lines. Morin induced DNA damage and reduced the DNA repair mechanism, a feature of chemoresistance. In addition, morin reduced the protein expressions of cell cycle regulators, such as cyclin D1, CDK4, cyclin E1, cyclin B1, and p-Rb, thereby halting cell cycle progression. Moreover, morin slightly reduced PARP and Bcl-xL expressions but left LC3-II and RIPK3 expressions unchanged. Annexin-V/7-AAD analysis showed morin increased 7-AAD positive cells and annexin-V positive cells among MDA-DR and MCF-DR cells, respectively. In addition, morin increased p-AMPK and p-LKB1 levels; and, thus, inhibited phosphorylation of the mTOR pathway, but decreased t-AMPK levels by inducing lysosomal degradation, and AICAR, an AMPK activator, reduced Raptor, cyclin D1, CDK4, cyclin E1 and phosphorylated, and total mTOR levels, indicating AMPK is a key player in inducing cell death. Also, morin modulated MAPK phosphorylation and attenuated p-Akt and p-GSK3αβ levels; and thus, inhibited cell survival. In addition, morin suppressed tumor growth in our MDA-DR xenografted mouse model. These findings indicate that morin is a potential treatment for Dox-resistant breast cancer and that it does so by inducing DNA damage and modulating the LKB1/AMPK/mTORC1 pathway, along with regulating the MAPK, and Akt/GSK3αβ signaling pathways.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arsenic-induced transition of thymic inflammation-to-fibrosis involves Stat3-Twist1 interaction: Melatonin to the rescue.","authors":"Ankur Das, Ankan Mitra, Sourav Ghosh, Swaimanti Sarkar, Palash Kumar Pal, Debasish Bandyopadhyay, Sreya Chattopadhyay","doi":"10.1002/biof.2110","DOIUrl":"https://doi.org/10.1002/biof.2110","url":null,"abstract":"<p><p>Groundwater arsenic is a notorious toxicant and exposure to environmentally relevant concentrations persists as a healthcare burden across the world. Arsenic has been reported to jeopardize the normal functioning of the immune system, but there are still gaps in the understanding of thymic T cell biology. Immunotoxic influence of arsenic in thymic integrity demands a potent restorative molecule. The objectives of this study were to examine key signaling cross-talks associated with arsenic-induced immune alterations in the thymus and propose melatonin as a potential candidate against immunological complications arising from arsenic exposure. Swiss albino mice were exposed to sodium arsenite (0.05 mg/L; in drinking water) and melatonin (IP:10 mg/kg BW) for 28 days. Melatonin successfully protected thymus from arsenic-mediated tissue degeneration and maintained immune homeostasis including T cell maturation and proliferation by mitigating oxidative stress through Nrf2 upregulation. Additionally, melatonin exerted ameliorative effect against arsenic-induced apoptosis and inflammation by inhibiting p53-mediated mitochondrial cell death pathway and NF-κB-p65/STAT3-mediated proinflammatory pathway, respectively. For the first time, we showed that arsenic-induced profibrotic changes were inhibited by melatonin through targeting of inflammation-associated EMT. Our findings clearly demonstrate that melatonin can be a viable and promising candidate in combating arsenic-induced immune toxicity with no collateral damage, making it an important research target.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fisetin is a selective adenosine triphosphate-competitive inhibitor for mitogen-activated protein kinase kinase 4 to inhibit lipopolysaccharide-stimulated inflammation.","authors":"Ziyu He, Takuhiro Uto, Shunsuke Tanigawa, Kozue Sakao, Takuma Kumamoto, Kun Xie, Xuchi Pan, Shusong Wu, Yili Yang, Masaharu Komatsu, De-Xing Hou","doi":"10.1002/biof.2108","DOIUrl":"https://doi.org/10.1002/biof.2108","url":null,"abstract":"<p><p>The mitogen-activated protein kinase kinase 4 (MKK4), a member of the MAP kinase kinase family, directly phosphorylates and activates the c-Jun NH2-terminal kinases (JNK), in response to proinflammatory cytokines and cellular stresses. Regulation of the MKK4 activity is considered to be a novel approach for the prevention and treatment of inflammation. The aim of this study was to identify whether fisetin, a potential anti-inflammatory compound, targets MKK4-JNK cascade to inhibit lipopolysaccharide (LPS)-stimulated inflammatory response. RAW264 macrophage pretreated with fisetin following LPS stimulation was used as a cell model to investigate the transactivation and expression of related-inflammatory genes by transient transfection assay, electrophoretic mobility shift assay (EMSA), or enzyme-linked immunosorbent assay (ELISA), and cellular signaling as well as binding of related-signal proteins by Western blot, pull-down assay and kinase assay, and molecular modeling. The transactivation and expression of cyclooxygenase-2 (COX-2) gene as well as prostaglandin E₂ (PGE₂) secretion induced by LPS were inhibited by fisetin in a dose-dependent manner. Signaling transduction analysis demonstrated that fisetin selectively inhibited MKK4-JNK1/2 signaling to suppress the phosphorylation of transcription factor AP-1 without affecting the NF-κB and Jak2-Stat3 signaling as well as the phosphorylation of Src, Syk, and TAK1. Furthermore, in vitro and ex vivo pull-down assay using cell lysate or purified protein demonstrated that fisetin could bind directly to MKK4. Molecular modeling using the Molecular Operating Environment™ software indicated that fisetin docked into the ATP-binding pocket of MKK4 with a binding energy of -71.75 kcal/mol and formed a 1.70 Å hydrogen bound with Asp247 residue of MKK4. The IC₅₀ of fisetin against MKK4 was estimated as 2.899 μM in the kinase assay, and the ATP-competitive effect was confirmed by ATP titration. Taken together, our data revealed that fisetin is a potent selective ATP-competitive MKK4 inhibitor to suppress MKK4-JNK1/2-AP-1 cascade for inhibiting LPS-induced inflammation.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine chloride loaded nano-PEGylated liposomes attenuates imidacloprid-induced neurotoxicity by inhibiting NLRP3/Caspase-1/GSDMD-mediated pyroptosis.","authors":"Walaa Bayoumie El Gazzar, Amina A Farag, Mohamed Samir, Heba Bayoumi, Heba S Youssef, Yasmin Mohammed Marei, Shimaa K Mohamed, Azza M Marei, Reham M Abdelfatah, Manal Moustafa Mahmoud, Elshaimaa Ahmed Fahmy Aboelkomsan, Eman Kamel M Khalfallah, Hala Magdy Anwer","doi":"10.1002/biof.2107","DOIUrl":"https://doi.org/10.1002/biof.2107","url":null,"abstract":"<p><p>Concerns have been expressed about imidacloprid (IMI), one of the most often used pesticides, and its potential neurotoxicity to non-target organisms. Chronic neuroinflammation is central to the pathology of several neurodegenerative disorders. Hence, exploring the molecular mechanism by which IMI would trigger neuroinflammation is particularly important. This study examined the neurotoxic effects of oral administration of IMI (45 mg/kg/day for 30 days) and the potential neuroprotective effect of berberine (Ber) chloride loaded nano-PEGylated liposomes (Ber-Lip) (10 mg/kg, intravenously every other day for 30 days) using laboratory rat. The histopathological changes, anti-oxidant and oxidative stress markers (GSH, SOD, and MDA), proinflammatory cytokines (IL1β and TNF-α), microglia phenotype markers (CD86 and iNOS for M1; CD163 for M2), the canonical pyroptotic pathway markers (NLRP3, caspase-1, GSDMD, and IL-18) and Alzheimer's disease markers (Neprilysin and beta amyloid [Aβ] deposits) were assessed. Oral administration of IMI resulted in apparent cerebellar histopathological alterations, oxidative stress, predominance of M1 microglia phenotype, significantly upregulated NLRP3, caspase-1, GSDMD, IL-18 and Aβ deposits and significantly decreased Neprilysin expression. Berberine reduced the IMI-induced aberrations in the measured parameters and improved the IMI-induced histopathological and ultrastructure alterations brought on by IMI. This study highlights the IMI neurotoxic effect and its potential contribution to the development of Alzheimer's disease and displayed the neuroprotective effect of Ber-Lip.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intramuscular administration of fractalkine modulates mitochondrial properties and promotes fast glycolytic phenotype.","authors":"Gourabamani Swalsingh, Punyadhara Pani, Unmod Senapati, Bijayashree Sahu, Sunil Pani, Benudhara Pati, Subhasmita Rout, Naresh C Bal","doi":"10.1002/biof.2092","DOIUrl":"https://doi.org/10.1002/biof.2092","url":null,"abstract":"<p><p>A newly categorized myokine called fractalkine (CX3CL1) has been associated with divergent conditions such as obesity, tissue inflammation, and exercise. CX3CL1 works through specific membrane-bound receptors (CX3CR1) found in various tissues including skeletal muscles. Studies indicate CX3CL1 induces muscles to uptake energy substrates thereby improving glucose utilization and countering diabetes. Here, we tested if the administration of purified CX3CL1 directly into mice skeletal muscles affects its histoarchitecture, mitochondrial activity, and expression of metabolic proteins. We analyzed four muscles: two upper-limb (quadriceps, hamstrings) and two lower-limb (tibialis anterior, gastrocnemius), contralateral leg muscles were taken as controls. The effects of CX3CL1 treatment on histoarchitecture, mitochondrial activity, and expression of metabolic proteins in muscles were characterized. We used histochemical staining succinate dehydrogenase (SDH)/cytochrome c oxidase (COX), myosin ATPase, alkaline phosphatase (ALP) to evaluate the mitochondrial activity, fiber types, and vascularization in the muscles, respectively. Western blotting was used to evaluate the expression of proteins associated with mitochondrial metabolism (OXPHOS), glycolysis, and vascularization. Overall, this study indicates CX3CL1 primarily modulates mitochondrial metabolism and shifts substrate preference toward glucose in the skeletal muscle. Evidence also supports that CX3CL1 stimulates the relative composition of fast fiber types, influencing selection of energy substrates in the skeletal muscle.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Systemic inflammation and oxidative stress induced by inhaled Paraquat in rat improved by Carvacrol, possible role of PPARγ receptors","authors":"","doi":"10.1002/biof.2093","DOIUrl":"10.1002/biof.2093","url":null,"abstract":"<p><b>RETRACTION</b>: F. Amin, A. Memarzia, H. K. Rad, F. Shakeri and M. H. Boskabady, “Systemic Inflammation and Oxidative Stress Induced by Inhaled Paraquat in Rat Improved by Carvacrol, Possible Role of PPARγ Receptors,” <i>Biofactors</i> 47, no. 5 (2021): 778–787, https://doi.org/10.1002/biof.1761.</p><p>The above article, published online on 05 June 2021 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Irene Diaz-Moreno; the International Union of Biochemistry and Molecular Biology; and Wiley Periodicals LLC. The retraction has been agreed due to considerable overlap with previously published articles from a similar group of authors. As a result, the editors consider a significant portion of the results reported in this study redundant. The authors disagree with the retraction.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.2093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ErbB2-NOTCH1 axis controls autophagy in cardiac cells.","authors":"Francesca Fortini, Francesco Vieceli Dalla Sega, Edoardo Lazzarini, Giorgio Aquila, Polina Sysa-Shah, Edoardo Bertero, Alessia Ascierto, Paolo Severi, Achille Wilfred Ouambo Talla, Alessio Schirone, Kathleen Gabrielson, Giampaolo Morciano, Simone Patergnani, Gaia Pedriali, Paolo Pinton, Roberto Ferrari, Elena Tremoli, Pietro Ameri, Paola Rizzo","doi":"10.1002/biof.2091","DOIUrl":"https://doi.org/10.1002/biof.2091","url":null,"abstract":"<p><p>Although the epidermal growth factor receptor 2 (ErbB2) and Notch1 signaling pathways have both significant roles in regulating cardiac biology, their interplay in the heart remains poorly investigated. Here, we present evidence of a crosstalk between ErbB2 and Notch1 in cardiac cells, with effects on autophagy and proliferation. Overexpression of ErbB2 in H9c2 cardiomyoblasts induced Notch1 activation in a post-transcriptional, p38-dependent manner, while ErbB2 inhibition with the specific inhibitor, lapatinib, reduced Notch1 activation. Moreover, incubation of H9c2 cells with lapatinib resulted in stalled autophagic flux and decreased proliferation, consistent with the established cardiotoxicity of this and other ErbB2-targeting drugs. Confirming the findings in H9c2 cells, exposure of primary neonatal mouse cardiomyocytes to exogenous neuregulin-1, which engages ErbB2, stimulated proliferation, and this effect was abrogated by concomitant inhibition of the enzyme responsible for Notch1 activation. Furthermore, the hearts of transgenic mice specifically overexpressing ErbB2 in cardiomyocytes had increased levels of active Notch1 and of Notch-related genes. These data expand the knowledge of ErbB2 and Notch1 functions in the heart and may allow better understanding the mechanisms of the cardiotoxicity of ErbB2-targeting cancer treatments.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the potential: Extracellular vesicles from plant cell suspension cultures as a promising source.","authors":"Oğuz Kaan Kırbaş, Derya Sağraç, Özgün Cem Çiftçi, Gökçeçiçek Özdemir, Dilek Öztürkoğlu, Batuhan Turhan Bozkurt, Ümit Cem Derman, Ezgi Taşkan, Pakize Neslihan Taşlı, Bahar Soğutmaz Özdemir, Fikrettin Şahin","doi":"10.1002/biof.2090","DOIUrl":"https://doi.org/10.1002/biof.2090","url":null,"abstract":"<p><p>Extracellular vesicles are secreted by all eukaryotic cells and they have an important role in intercellular signaling. Plant extracellular vesicles (PEVs) are a novel area of research that has gained attention due to their potential implications in biomolecule transport and therapeutic applications. PEVs are lipid bilayer-enclosed structures that contain a diverse cargo of biomolecules such as proteins and lipids. Moreover, it is known that PEVs have a noticeable therapeutic potential for various conditions such as inflammation and oxidative stress. However, there are critical problems such as removing the endosomes and plant-derived biomolecules that decrease the standardization and therapeutic efficacy of PEVs. In our study, the aim was to characterize plant cell suspension-derived extracellular vesicles (PCSEVs) obtained from two different plant cell suspension cultures: Stevia rebaudiana and Vaccaria hispanica. These vesicles were isolated using ultrafiltration and characterized with nanoparticle tracking analysis (NTA) and atomic force microscopy (AFM). The molecular composition of PCSEVs was profiled and the cellular uptake assay was performed. Our results demonstrated that PCSEVs have a spherical shape, less than 200 nm. In the fatty acid analysis, the primary components in PCSEVs were palmitic acid, linoleic acid, and cis-vaccenic acid. The protein content of Stevia rebaudiana-derived EVs (SDEVs) was largely associated with proteins involved in extracellular structures and functions. Conversely, Vaccaria hispanica-derived EVs (HDEVs) displayed a higher presence of cytosolic proteins. These findings contribute to the understanding of PCSEVs and open up potential avenues in extracellular vesicle research, pointing to promising prospects for future innovations in various fields.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perillaldehyde alleviates polyQ-induced neurodegeneration through the induction of autophagy and mitochondrial UPR in Caenorhabditis elegans.","authors":"Minglv Fang, Ying Liu, Xiaoyan Gao, Jing Yu, Xiaohui Tu, Xueying Mo, Huanhu Zhu, Yan Zou, Cheng Huang, Shengjie Fan","doi":"10.1002/biof.2089","DOIUrl":"https://doi.org/10.1002/biof.2089","url":null,"abstract":"<p><p>Huntington's disease (HD) is a fatal neurodegenerative disease associated with autophagy disorder and mitochondrial dysfunction. Here, we identified therapeutic potential of perillaldehyde (PAE), a monoterpene compound obtained from Perilla frutescens (L.) Britt., in the Caenorhabditis elegans (C. elegans) model of HD, which included lifespan extension, healthspan improvement, decrease in polyglutamine (polyQ) aggregation, and preservation of mitochondrial network. Further analyses indicated that PAE was able to induce autophagy and mitochondrial unfolded protein reaction (UPR^mt) activation and positively regulated expression of associated genes. In lgg-1 RNAi C. elegans or C. elegans with UPR^mt-related genes knockdown, the effects of PAE treatment on polyQ aggregation or rescue polyQ-induced toxicity were attenuated, suggesting that its neuroprotective activity depended on autophagy and UPR^mt. Moreover, we found that pharmacological and genetic activation of UPR^mt generally protected C. elegans from polyQ-induced cytotoxicity. Finally, PAE promoted serotonin synthesis by upregulating expression of TPH-1, and serotonin synthesis and neurosecretion were required for PAE-mediated UPR^mt activation and its neuroprotective activity. In conclusion, PAE is a potential therapy for polyQ-related diseases including HD, which is dependent on autophagy and cell-non-autonomous UPR^mt activation.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}