Melatonin ameliorates Parkinson’s disease via regulating microglia polarization in a RORα‐dependent pathway

Li, Jingwen; Liu, Hanshu; Wang, Xinyi; Xia, Yun; Huang, Jinsha; Wang, Tao; Lin, Zhicheng; Xiong, Nian

doi:10.1038/s41531-022-00352-5

Cited by 22 publications

(15 citation statements)

References 71 publications

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“…63 Li et al discovered that MEL promoted MG polarization to M2 through STAT signaling pathway, therefore inhibiting neuroinflammation in parkinsonism-related symptoms. 64 In our study, we found that MEL influenced MG polarization probably through RhoA/ROCK signaling pathway. When neurons are injured, Rho is activated and induces the atrophy of growth cone and axon regeneration disorder.…”

Section: Discussionsupporting

confidence: 49%

“…Besides, Zhou et al found that MEL shifted M1 MG toward M2 through MT1/JAK2/STAT3/telomerase pathway and ameliorated periventricular white matter injury in rats 63 . Li et al discovered that MEL promoted MG polarization to M2 through STAT signaling pathway, therefore inhibiting neuroinflammation in parkinsonism‐related symptoms 64 …”

Section: Discussionmentioning

confidence: 99%

“… 63 Li et al discovered that MEL promoted MG polarization to M2 through STAT signaling pathway, therefore inhibiting neuroinflammation in parkinsonism‐related symptoms. 64 …”

Section: Discussionmentioning

confidence: 99%

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Melatonin regulates microglial polarization to M2 cell via RhoA/ROCK signaling pathway in epilepsy

Shan

et al. 2023

Immunity Inflam & Disease

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Background: Melatonin (MEL), an endogenous hormone, has been widely investigated in neurological diseases. Microglia (MG), a resident immunocyte localizing in central nervous system is reported to play important functions in the animal model of temporal lobe epilepsy (TLE). Some evidence showed that MEL influenced activation of MG, but the detailed model of action that MEL plays in remains uncertain.Methods: In this study, we established a model of TLE in mice by stereotactic injection of kainic acid (KA). We treated the mice with MEL. Lipopolysaccharide, ROCK2-knockdown (ROCK-KD) and -overexpression (ROCK-OE) of lentivirus-treated cells were used in cell experiments to simulate an in vitro inflammatory model. Results:The results of electrophysiological tests showed that MEL reduced frequency and severity of seizure. The results of behavioral tests indicated MEL improved cognition, learning, and memory ability. Histological evidences demonstrated a significant reduction of neuronal death in the hippocampus.In vivo study showed that MEL changed the polarization status of MG from a proinflammatory M1 phenotype to an anti-inflammatory M2 phenotype by inversely regulating the RhoA/ROCK signaling pathway. In cytological study, we found that MEL had a significant protective effect in LPS-treated BV-2 cells and ROCK-KD cells, while the protective effect of MEL was significantly attenuated in ROCK-OE cells. Conclusion:MEL played an antiepileptic role in the KA-induced TLE modeling mice both in behavioral and histological levels, and changed MG polarization status by regulating the RhoA/ROCK signaling pathway.

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Section: Discussionsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

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Melatonin regulates microglial polarization to M2 cell via RhoA/ROCK signaling pathway in epilepsy

Shan

et al. 2023

Immunity Inflam & Disease

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“…17 It modulates microglial polarization and reduces neuroinflammation through its antioxidant and antistress properties. 18 Melatonin acts on G-protein-coupled receptors, mainly MT1 and MT2. 19 Altered microglial metabolism and increased neuroinflammation in PD are associated with MT1 deficiency.…”

Section: Introductionmentioning

confidence: 99%

“…Melatonin, a hormone secreted by the pineal gland, has potent neuroprotective effects in PD 17 . It modulates microglial polarization and reduces neuroinflammation through its antioxidant and antistress properties 18 . Melatonin acts on G‐protein‐coupled receptors, mainly MT1 and MT2 19 .…”

Section: Introductionmentioning

confidence: 99%

Melatonin MT1 receptors regulate the Sirt1/Nrf2/Ho‐1/Gpx4 pathway to prevent α‐synuclein‐induced ferroptosis in Parkinson's disease

Lv,

Tao,

Yao

et al. 2024

Journal of Pineal Research

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons and aggregation of α‐synuclein (α‐syn). Ferroptosis, a form of cell death induced by iron accumulation and lipid peroxidation, is involved in the pathogenesis of PD. It is unknown whether melatonin receptor 1 (MT1) modulates α‐syn and ferroptosis in PD. Here, we used α‐syn preformed fibrils (PFFs) to induce PD models in vivo and in vitro. In PD mice, α‐syn aggregation led to increased iron deposition and ferroptosis. MT1 knockout exacerbated these changes and resulted in more DA neuronal loss and severe motor impairment. MT1 knockout also suppressed the Sirt1/Nrf2/Ho1/Gpx4 pathway, reducing resistance to ferroptosis, and inhibited expression of ferritin Fth1, leading to more release of ferrous ions. In vitro experiments confirmed these findings. Knockdown of MT1 enhanced α‐syn PFF‐induced intracellular α‐syn aggregation and suppressed expression of the Sirt1/Nrf2/Ho1/Gpx4 pathway and Fth1 protein, thereby aggravating ferroptosis. Conversely, overexpression of MT1 reversed these effects. Our findings reveal a novel mechanism by which MT1 activation prevents α‐syn‐induced ferroptosis in PD, highlighting the neuroprotective role of MT1 in PD.

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An Expanded Narrative Review of Neurotransmitters on Alzheimer’s Disease: The Role of Therapeutic Interventions on Neurotransmission

Akyuz,

Arulsamy,

Aslan

et al. 2024

Mol Neurobiol

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles are the key players responsible for the pathogenesis of the disease. The accumulation of Aβ plaques and tau affect the balance in chemical neurotransmitters in the brain. Thus, the current review examined the role of neurotransmitters in the pathogenesis of Alzheimer’s disease and discusses the alterations in the neurochemical activity and cross talk with their receptors and transporters. In the presence of Aβ plaques and neurofibrillary tangles, changes may occur in the expression of neuronal receptors which in turn triggers excessive release of glutamate into the synaptic cleft contributing to cell death and neuronal damage. The GABAergic system may also be affected by AD pathology in a similar way. In addition, decreased receptors in the cholinergic system and dysfunction in the dopamine neurotransmission of AD pathology may also contribute to the damage to cognitive function. Moreover, the presence of deficiencies in noradrenergic neurons within the locus coeruleus in AD suggests that noradrenergic stimulation could be useful in addressing its pathophysiology. The regulation of melatonin, known for its effectiveness in enhancing cognitive function and preventing Aβ accumulation, along with the involvement of the serotonergic system and histaminergic system in cognition and memory, becomes remarkable for promoting neurotransmission in AD. Additionally, nitric oxide and adenosine-based therapeutic approaches play a protective role in AD by preventing neuroinflammation. Overall, neurotransmitter-based therapeutic strategies emerge as pivotal for addressing neurotransmitter homeostasis and neurotransmission in the context of AD. This review discussed the potential for neurotransmitter-based drugs to be effective in slowing and correcting the neurodegenerative processes in AD by targeting the neurochemical imbalance in the brain. Therefore, neurotransmitter-based drugs could serve as a future therapeutic strategy to tackle AD.

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Melatonin ameliorates Parkinson’s disease via regulating microglia polarization in a RORα‐dependent pathway

Cited by 22 publications

References 71 publications

Melatonin regulates microglial polarization to M2 cell via RhoA/ROCK signaling pathway in epilepsy

Melatonin regulates microglial polarization to M2 cell via RhoA/ROCK signaling pathway in epilepsy

Melatonin MT1 receptors regulate the Sirt1/Nrf2/Ho‐1/Gpx4 pathway to prevent α‐synuclein‐induced ferroptosis in Parkinson's disease

An Expanded Narrative Review of Neurotransmitters on Alzheimer’s Disease: The Role of Therapeutic Interventions on Neurotransmission

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