Activation of melatonin receptor 1 by CRISPR‐Cas9 activator ameliorates cognitive deficits in an Alzheimer's disease mouse model

Park, Hanseul; Kim, Jong-Pil

doi:10.1111/jpi.12787

Cited by 14 publications

(8 citation statements)

References 69 publications

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“…p-values <0.05 were considered statistically significant (*p < 0.05 and **p < 0.01). No statistical methods were used to pre-determine sample sizes; however, our sample sizes were similar to those reported in previous publications [49][50][51][52][53][54][55][56] . Data collection and analysis were randomized and blinded.…”

Section: Discussionmentioning

confidence: 66%

Single-cell RNA-sequencing identifies disease-associated oligodendrocytes in male APP NL-G-F and 5XFAD mice

et al. 2023

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Alzheimer’s disease (AD) is associated with progressive neuronal degeneration as amyloid-beta (Aβ) and tau proteins accumulate in the brain. Glial cells were recently reported to play an important role in the development of AD. However, little is known about the role of oligodendrocytes in AD pathogenesis. Here, we describe a disease-associated subpopulation of oligodendrocytes that is present during progression of AD-like pathology in the male AppNL-G-F and male 5xFAD AD mouse brains and in postmortem AD human brains using single-cell RNA sequencing analysis. Aberrant Erk1/2 signaling was found to be associated with the activation of disease-associated oligodendrocytes (DAOs) in male AppNL-G-F mouse brains. Notably, inhibition of Erk1/2 signaling in DAOs rescued impaired axonal myelination and ameliorated Aβ-associated pathologies and cognitive decline in the male AppNL-G-F AD mouse model.

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Section: Discussionmentioning

confidence: 66%

Single-cell RNA-sequencing identifies disease-associated oligodendrocytes in male APP NL-G-F and 5XFAD mice

et al. 2023

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“…Animal experiments showed that melatonin can inhibit expressions of amyloid-β protein in the hippocampal area of model rats with senile dementia [ 44 ]. Activation of the type 1 melatonin receptor modulated anti-amyloidogenic and anti-inflammatory roles in AD mice brain and improved the cognitive deficits [ 45 ]. Shift work was also associated with abnormalities in brain structure that had been observed in dementia pathophysiology, giving a hint of the underlying brain mechanisms of shift work on dementia risk [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Association of shift work with incident dementia: a community-based cohort study

Liao

Dong

Deng

et al. 2022

BMC Med

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Background Some observational studies had found that shift work would increase risks of metabolic disorders, cancers, and cardiovascular diseases, but there was no homogeneous evidence of such an association between shift work and incident dementia. This study aimed to investigate whether shift work would increase the risk of dementia in a general population. Methods One hundred seventy thousand seven hundred twenty-two employed participants without cognitive impairment or dementia at baseline recruited between 2006 and 2010 were selected from the UK Biobank cohort study. Follow-up occurred through June 2021. Shift work status at baseline was self-reported by participants and they were categorized as non-shift workers or shift workers. Among shift workers, participants were further categorized as night shift workers or shift but non-night shift workers. The primary outcome was all-cause dementia in a time-to-event analysis, and the secondary outcomes were subtypes of dementia, including Alzheimer’s disease, vascular dementia, and other types of dementia. Results In total, 716 dementia cases were observed among 170,722 participants over a median follow-up period of 12.4 years. Shift workers had an increased risk of all-cause dementia as compared with non-shift workers after multivariable adjustment (hazard ratio [HR], 1.30, 95% confidence interval [CI], 1.08–1.58); however, among shift workers, night shift work was not associated with the risk of dementia (HR, 1.04, 95% CI, 0.73–1.47). We found no significant interaction between shift work and genetic predisposition to dementia on the primary outcome (P for interaction = 0.77). Conclusions Shift work at baseline was associated with an increased risk of all-cause dementia. Among shift workers, there was no significant association between night shift work and the risk of dementia. The increased incidence of dementia in shift workers did not differ between participants in different genetic risk strata for dementia.

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“…24,25 Melatonin is a potent free radical scavenger that has demonstrated beneficial effects in animal models of acute injuries, such as spinal cord injury (SCI), and chronic injuries, such as Parkinson's disease related to the CNS. [26][27][28][29][30] As a chronic nontraumatic SCI, we inferred that melatonin may be effective in treating CSM. In this in vivo experiment, we aimed to evaluate whether melatonin inhibited neuronal apoptosis by restoring ER homeostasis, alleviating ER stress, and promoting ERphagy, ultimately improving neurological function in a rat model of chronic cervical cord compression.…”

Section: Introductionmentioning

confidence: 95%

“…Melatonin is a potent free radical scavenger that has demonstrated beneficial effects in animal models of acute injuries, such as spinal cord injury (SCI), and chronic injuries, such as Parkinson's disease related to the CNS 26–30 . As a chronic nontraumatic SCI, we inferred that melatonin may be effective in treating CSM.…”

Section: Introductionmentioning

confidence: 99%

Melatonin restores endoplasmic reticulum homeostasis to protect injured neurons in a rat model of chronic cervical cord compression

Yao

Zhu

et al. 2023

Journal of Pineal Research

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Cervical spondylotic myelopathy (CSM) refers to a chronic injury of the cervical cord caused by cervical intervertebral disc degeneration. Endoplasmic reticulum (ER) homeostasis is essential to counteract neuronal apoptosis. ER stress, an integral part of ER homeostasis, was observed in a rat model of chronic cervical cord compression in our previous study. However, the correlation between ER homeostasis and CSM remains unknown. The antioxidant melatonin is known to exert therapeutic effects in acute spinal cord injury, but the specific effects and their potential mechanisms in the pathological processes of CSM require further exploration. The present study hypothesized that ER homeostasis is essential for neuronal apoptosis in the CSM and that melatonin maintains this homeostasis. The results showed that ER stress led to neuronal apoptosis in rats with chronic cervical cord compression. Conversely, melatonin attenuates protein kinase R‐like ER kinase‐eukaryotic initiation factor 2α‐C/EBP‐homologous protein, inositol‐requiring enzyme 1, and transcription factor 6 signaling pathways to release ER stress and prevents Bax translocation to the mitochondrion, thereby promoting motor recovery and protecting neurons in vivo. It also rescued primary rat cortical neurons from ER stress‐induced glutamate toxicity in vitro. Moreover, melatonin remodels the ER morphology and restores homeostasis via ER‐phagy in injured neurons. FAM134B, CCPG1, RTN3, and Sec. 62 are four known ER‐phagy receptors. In this study, Sec. 62 was identified as a key melatonin factor in promoting ER‐phagy and restoring ER homeostasis in damaged neurons in vivo and in vitro. In conclusion, melatonin suppresses neuronal apoptosis by reducing ER stress and promoting ER‐phagy to restore ER morphology and homeostasis. The current results suggested that melatonin is a promising treatment for CSM owing to its restorative effect on ER homeostasis; however, well‐designed randomized controlled trials must be carried out to further investigate its clinical effects.

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Activation of melatonin receptor 1 by CRISPR‐Cas9 activator ameliorates cognitive deficits in an Alzheimer's disease mouse model

Cited by 14 publications

References 69 publications

Single-cell RNA-sequencing identifies disease-associated oligodendrocytes in male APP NL-G-F and 5XFAD mice

Single-cell RNA-sequencing identifies disease-associated oligodendrocytes in male APP NL-G-F and 5XFAD mice

Association of shift work with incident dementia: a community-based cohort study

Melatonin restores endoplasmic reticulum homeostasis to protect injured neurons in a rat model of chronic cervical cord compression

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