Melatonin attenuates branch chain fatty acid induced apoptosis mediated neurodegeneration

Chaudhary, Shaista; Sahu, Upasana; Parvez, Suhel

doi:10.1002/tox.23055

Cited by 7 publications

(5 citation statements)

References 72 publications

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“…48 Finally, VPA may enhance neurodegeneration through free oxygen radicals. 49,50 In humans, however, it is not clear which of the aforementioned mechanisms is the major determinant of VPA adverse effects. It is also not clear what neural circuits are the most affected by VPA.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it interferes with gene expression by downregulating the transcription of genes involved in synaptic plasticity and neuronal survival 46,47 and by acting as a histone deacetylase, thus unpacking DNA from histones 48 . Finally, VPA may enhance neurodegeneration through free oxygen radicals 49,50 . In humans, however, it is not clear which of the aforementioned mechanisms is the major determinant of VPA adverse effects.…”

Section: Discussionmentioning

confidence: 99%

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Tremor and Movement Slowness Are Two Unrelated Adverse Effects Induced by Valproate Intake

Biase

Paparella

Angelini

et al. 2022

Movement Disord Clin Pract

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Background To date, only a few clinical and neurophysiological studies have assessed the features of valproate‐induced tremor (VIT), and whether valproate (VPA) affects voluntary movements is underinvestigated. Objective To better characterize the clinical and neurophysiological features of VIT in patients with epilepsy and the effect of VPA on the execution of voluntary movement. Methods We tested 29 patients with VIT (13 taking VPA alone and 16 taking VPA plus other antiepileptics). Patients underwent a neurological examination, video recordings and kinematic assessments of postural, kinetic, and resting upper limb tremor using a motion analysis system. Movement execution was tested by kinematic assessment of finger tapping. Data of patients with VIT were compared with those of 13 patients with epilepsy taking VPA but without tremor, 13 patients with epilepsy who were not on VPA treatment, 20 patients with Parkinson's disease (PD), and 20 healthy controls (HCs). Results Clinical and kinematic evaluations showed that tremor in patients taking VPA alone was less severe than tremor in patients taking VPA plus other antiepileptics. All patients taking VPA, regardless of the presence of tremor, performed slower finger tapping compared with HCs, similar to what was observed in PD, although with no sequence effect. Patients with epilepsy without VPA showed a normal motor performance. Conclusions Tremor and movement slowness are motor signs induced by VPA. VIT severity is exacerbated when VPA is taken in combination with other antiepileptics. VPA‐induced slowness occurs regardless of tremor, may precede tremor development, and is not attributed to epilepsy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tremor and Movement Slowness Are Two Unrelated Adverse Effects Induced by Valproate Intake

Biase

Paparella

Angelini

et al. 2022

Movement Disord Clin Pract

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“…Melatonin is a hormone produced within the body, primarily generated in the pineal gland, playing a vital role in regulating the biological clock and sleep patterns 17–19 . Recent research has discovered that melatonin also possesses antioxidant, anti‐inflammatory, and anti‐apoptotic properties, thus gaining widespread attention in the study of various diseases, such as neurodegenerative diseases, cardiovascular diseases, and tumors.…”

Section: Discussionmentioning

confidence: 99%

Melatonin alleviates ischemic stroke by inhibiting ferroptosis through the CYP1B1/ACSL4 pathway

Sun,

Jin,

et al. 2024

Environmental Toxicology

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This study utilized middle cerebral artery occlusion (MCAO) mouse models and HT‐22 cell oxygen and glucose deprivation/reoxygenation (OGD/R) models to investigate the therapeutic effects of melatonin on ischemic brain injury. In the experiments, MCAO mice were treated with 5 and 10 mg/kg doses of melatonin, and H‐T22 cells underwent OGD/R treatment and were administered different concentrations of melatonin. The results showed that melatonin significantly reduced ischemic brain area, neural damage, cerebral edema, and neuronal apoptosis in MCAO mice. In the HT‐22 cell model, melatonin also improved cell proliferation ability, reduced apoptosis, and ROS production. Further mechanistic studies found that melatonin exerts protective effects by inhibiting ferroptosis, an iron‐dependent form of regulated cell death, through regulation of the ACSL4/CYP1B1 pathway. In MCAO mice, melatonin decreased lipid peroxidation, ROS production, and ACSL4 protein expression. Overexpression of CYP1B1 increased ACSL4 ubiquitination and degradation, thereby increasing cell tolerance to ferroptosis, reducing ACSL4 protein levels, and decreasing ROS production. CYP1B1 knockdown obtained opposite results. The CYP1B1 metabolite 20‐HETE induces expression of the E3 ubiquitin ligase FBXO10 by activating PKC signaling, which promotes ACSL4 degradation. In the OGD/R cell model, inhibition of CYP1B1 expression reversed the therapeutic effects of melatonin. In summary, this study demonstrates that melatonin protects the brain from ischemic injury by inhibiting ferroptosis through regulation of the ACSL4/CYP1B1 pathway, providing evidence for new therapeutic targets for ischemic brain injury.

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“…Moreover, short-chain fatty acids can improve the intestinal environment (Goverse et al, 2017 ; Melbye et al, 2019 ). Recent studies on short-chain fatty acids have also shown their vital roles in alleviating inflammation, preventing cancer, regulating cell apoptosis, and lowering cholesterol (Chaudhary et al, 2021 ; Jiao et al, 2021 ). Notably, thiram exposure also resulted in a significant increase in pathogenic bacteria, such as Aerococcus .…”

Section: Discussionmentioning

confidence: 99%

Pesticide thiram exposure alters the gut microbial diversity of chickens

2022

Front. Microbiol.

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Thiram is a major dithiocarbamate pesticide commonly found in polluted field crops, feed, and rivers. Environmental thiram exposure has been demonstrated to cause angiogenesis and osteogenesis disorders in chickens, but information regarding thiram influences on gut microbiota, apoptosis, and autophagy in chickens has been insufficient. Here, we explored the effect of thiram exposure on gut microbiota, apoptosis, and autophagy of chickens. Results demonstrated that thiram exposure impaired the morphology and structure of intestinal and liver tissues. Moreover, thiram exposure also triggered liver apoptosis and autophagy. The gut microbiota in chickens exposed to thiram exhibited a significant decline in alpha diversity, accompanied by significant shifts in taxonomic compositions. Bacterial taxonomic analysis indicated that thiram exposure causes a significant reduction in the levels of eight genera, as well as a significant increase in the levels of two phyla and 10 genera. Among decreased bacterial genera, seven genera even cannot be observed in the thiram-induced chickens. In summary, this study demonstrated that thiram exposure not only dramatically altered the gut microbial diversity and composition but also induced liver apoptosis and autophagy in chickens. Importantly, this study also conveyed a key message that the dysbiosis of gut microbiota may be one of the major pathways for thiram to exert its toxic effects.

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Melatonin attenuates branch chain fatty acid induced apoptosis mediated neurodegeneration

Cited by 7 publications

References 72 publications

Tremor and Movement Slowness Are Two Unrelated Adverse Effects Induced by Valproate Intake

Tremor and Movement Slowness Are Two Unrelated Adverse Effects Induced by Valproate Intake

Melatonin alleviates ischemic stroke by inhibiting ferroptosis through the CYP1B1/ACSL4 pathway

Pesticide thiram exposure alters the gut microbial diversity of chickens

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