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Background: The calcium channel has been considered to have great potential as a drug target for neuroprotective therapy in Parkinson's disease (PD), but previous studies yielded inconsistent results. Objectives: This study aimed to conduct a systematic review and meta-analysis to assess the relationship between using calcium channel blockers (CCBs) and the risk and progression of PD. Data sources and methods: The terms such as 'Parkinson's disease', 'PD', 'calcium channel blockers', and 'CCB' were used to search the literature published before 1 May 2023 in English databases, including PubMed, Embase, and Cochrane Library, for studies on CCB and PD. Data analysis was performed using Review Manager 5.3 software. Results: A total of 190 works of literature were preliminarily retrieved, and 177 works of literature were excluded by eliminating duplicates, reading abstracts, and reading full texts. A total of nine studies were finally included in the meta-analysis of the CCB and the risk of PD, and five studies were included in the systematic review of the CCB and the progression of PD. A total of 2,961,695 participants were included in the meta-analysis. The random-effects model was used for analysis due to significant heterogeneity. The main results of the meta-analysis showed that the use of CCB could reduce the risk of PD (relative risk 0.78, 95% confidence interval 0.62–0.99). Conclusion: CCB use was associated with a significantly reduced risk of PD. Whether CCB use has a disease-modifying effect on PD needs further study. Registration: PROSPERO: CRD42024508242. [ABSTRACT FROM AUTHOR]

Summary: We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C terminus and is associated with autism. Expressed as a single copy [Shank3(+/ΔC) mice], Shank3ΔC protein interacts with the wild-type (WT) gene product and results in >90% reduction of Shank3 at synapses. This “gain-of-function” phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of postsynaptic density proteins, spine morphology, and synapse number are unchanged in Shank3(+/ΔC) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/ΔC) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder. [ABSTRACT FROM AUTHOR]

Background: A number of studies have explored the link between neurodegenerative disorders (NDDs) and albumin, the main protein in human plasma. However, the results have been inconsistent, highlighting the necessity for a detailed systemic analysis., Methods: Utilizing data from the United Kingdom Biobank, we investigated the relationship between baseline levels of serum and urine albumin and the occurrence of common NDDs, including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and dementia, employing Cox proportional hazards regression analysis., Results: Our results reveal that elevated baseline serum albumin levels are linked to a decreased risk of developing dementia (beta = -0.024, SE = 0.004, p  < 0.001). Subgroup and interaction analyses highlighted the impact of factors like body mass index (BMI), age, and alcohol consumption on this relationship. Specifically, participants with higher BMI, younger age, or lower alcohol intake exhibited a stronger protective effect. On the other hand, a higher baseline level of urine microalbumin was connected to a slight increase in dementia risk (beta = 0.003, SE = 3.30E-04, p  < 0.001). No significant associations were found between albumin levels and the risk of PD or ALS., Conclusion: Our study underscores the potential role of serum albumin as a biomarker associated with reduced dementia risk. These findings contribute valuable insights into the understanding of albumin's impact on NDDs, suggesting its utility as a biomarker for dementia in clinical settings and informing future therapeutic strategies in clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cui, Li, Ke, Xiao, Wang, Jiang, Zheng, Lin, Huang and Shang.)

Background: Pain is one of the most common and troublesome symptoms of cancer. Although potential positive effects of acupuncture-point stimulation (APS) on cancer pain have been observed, knowledge regarding the selection of the optimal APS remains unclear because of a lack of evidence from head-to-head randomized controlled trials (RCTs)., Objective: This study aimed to carry out a network meta-analysis to compare the efficacy and safety of different APS combined with opioids in treating moderate to severe cancer pain and rank these methods for practical consideration., Methods: A comprehensive search of eight electronic databases was conducted to obtain RCTs involving different APS combined with opioids for moderate to severe cancer pain. Data were screened and extracted independently using predesigned forms. The quality of RCTs was appraised with the Cochrane Collaboration risk-of-bias tool. The primary outcome was the total pain relief rate. Secondary outcomes were the total incidence of adverse reactions, the incidence of nausea and vomiting, and the incidence of constipation. We applied a frequentist, fixed-effect network meta-analysis model to pool effect sizes across trials using rate ratios (RR) with their 95% confidence intervals (CI). Network meta-analysis was performed using Stata/SE 16.0., Results: We included 48 RCTs, which consisted of 4,026 patients, and investigated nine interventions. A network meta-analysis showed that a combination of APS and opioids was superior in relieving moderate to severe cancer pain and reducing the incidence of adverse reactions such as nausea, vomiting, and constipation compared to opioids alone. The ranking of total pain relief rates was as follows: fire needle (surface under the cumulative ranking curve (SUCRA) = 91.1%), body acupuncture (SUCRA = 85.0%), point embedding (SUCRA = 67.7%), auricular acupuncture (SUCRA = 53.8%), moxibustion (SUCRA = 41.9%), transcutaneous electrical acupoint stimulation (TEAS) (SUCRA = 39.0%), electroacupuncture (SUCRA = 37.4%), and wrist-ankle acupuncture (SUCRA = 34.1%). The ranking of total incidence of adverse reactions was as follows: auricular acupuncture (SUCRA = 23.3%), electroacupuncture (SUCRA = 25.1%), fire needle (SUCRA = 27.2%), point embedding (SUCRA = 42.6%), moxibustion (SUCRA = 48.2%), body acupuncture (SUCRA = 49.8%), wrist-ankle acupuncture (SUCRA = 57.8%), TEAS (SUCRA = 76.3%), and opioids alone (SUCRA = 99.7%)., Conclusions: APS seemed to be effective in relieving cancer pain and reducing opioid-related adverse reactions. Fire needle combined with opioids may be a promising intervention to reduce moderate to severe cancer pain as well as reduce opioid-related adverse reactions. However, the evidence was not conclusive. More high-quality trials investigating the stability of evidence levels of different interventions on cancer pain must be conducted., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier CRD42022362054., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Yuan, Zhang, Qiao, Cui, Wang and Feng.)

Rheb1 is an immediate early gene that functions to activate mammalian target of rapamycin (mTor) selectively in complex 1 (mTORC1). We have demonstrated previously that Rheb1 is essential for myelination in the CNS using a Nestin-Cre driver line that deletes Rheb1 in all neural cell lineages, and recent studies using oligodendrocyte-specific CNP-Cre have suggested a preferential role for mTORC1 is myelination in the spinal cord. Here, we examine the role of Rheb1/mTORC1 in mouse oligodendrocyte lineage using separate Cre drivers for oligodendrocyte progenitor cells (OPCs) including Olig1-Cre and Olig2-Cre as well as differentiated and mature oligodendrocytes including CNP-Cre and Tmem10-Cre. Deletion of Rheb1 in OPCs impairs their differentiation to mature oligodendrocytes. This is accompanied by reduced OPC cell-cycle exit suggesting a requirement for Rheb1 in OPC differentiation. The effect of Rheb1 on OPC differentiation is mediated by mTor since Olig1-Cre deletion of mTor phenocopies Olig1-Cre Rheb1 deletion. Deletion of Rheb1 in mature oligodendrocytes, in contrast, does not disrupt developmental myelination or myelin maintenance. Loss of Rheb1 in OPCs or neural progenitors does not affect astrocyte formation in gray and white matter, as indicated by the pan-astrocyte marker Aldh1L1. We conclude that OPC-intrinsic mTORC1 activity mediated by Rheb1 is critical for differentiation of OPCs to mature oligodendrocytes, but that mature oligodendrocytes do not require Rheb1 to make myelin or maintain it in the adult brain. These studies reveal mechanisms that may be relevant for both developmental myelination and impaired remyelination in myelin disease., (Copyright © 2014 the authors 0270-6474/14/3415764-15$15.00/0.)