A computational approach to analyzing the functional and structural impacts of Tripeptidyl-Peptidase 1 missense mutations in neuronal ceroid lipofuscinosis
In this study, we retrieved a mutational dataset screening for TPP1 protein from various databases (ClinVar, UniProt, HGMD). Fifty-six missense mutants were enumerated with computational methods to perceive the significant mutants (G475R and G501C) and correlated with clinical and literature data. A structure-based screening method was initiated to understand protein-ligand interaction and dynamic simulation. The docking procedure was performed for the native (3EDY) and mutant (G473R and G501C) structures with Gemfibrozil (gem), which lowers the lipid level, decreases the triglycerides amount in the blood circulation, and ...
Source: Metabolic Brain Disease - January 8, 2024 Category: Neurology Source Type: research
Ginger (Zingiber Officinale Roscoe) ameliorates ethanol-induced cognitive impairment by modulating NMDA and GABA-A receptors in rat hippocampus
AbstractBrain damage caused by ethanol abuse may lead to permanent damage, including severe dementia. The aim of this study was to investigate the effects of ginger powder on ethanol-induced cognitive disorders by examining oxidative damage and inflammation status, and the gene expression of N-methyl-D-aspartate (NMDA) and γ-Aminobutyric acid (GABA)-A receptors in the hippocampus of male rats. 24 adult male Sprague–Dawley rats were allocated randomly to four groups as follows control, ethanol (4g/kg/day, by gavage), ginger (1g/kg/day, by gavage), and ginger-ethanol. At the end of the study, memory and learning were eval...
Source: Metabolic Brain Disease - January 1, 2024 Category: Neurology Source Type: research
Andrographolide inhibits the activation of spinal microglia and ameliorates mechanical allodynia
In this study, we observed that Andro attenuated mechanical allodynia in inflammatory pain mice induced by injecting complete Freund ’s adjuvant (CFA) into the right hind paws. This analgesic effect of Andro is mainly dependent on its inhibition of microglial overactivation and the release of proinflammatory cytokines (TNF and IL-1β) in lumbar spinal cords of inflammatory pain model mice. More importantly, our data in vivo and in vitro revealed a negative role for Andro in regulating the TLR4/NF-κB signaling pathway, which might contribute to the inhibition of spinal microglial activation and proinflammatory cytokines ...
Source: Metabolic Brain Disease - January 1, 2024 Category: Neurology Source Type: research
Plasma metabolomics reveals the intervention mechanism of different types of exercise on chronic unpredictable mild stress-induced depression rat model
This study provides a powerful analytical tool to study the mechanism of the antidepressant effect of exercise, and provides an important method and basis for the early diagnosis, prevention and treatment of depression. (Source: Metabolic Brain Disease)
Source: Metabolic Brain Disease - January 1, 2024 Category: Neurology Source Type: research
Combination chemotherapy in rodents: a model for chemotherapy-induced neuropathic pain and pharmacological screening
AbstractChemotherapy-induced neuropathic pain (CINP) remains a therapeutic challenge, with no US-FDA approved drugs or effective treatments available. Despite significant progress in unravelling the pathophysiology of CINP, the clinical translation of this knowledge into tangible outcome remains elusive. Here, we employed behavioural and pharmacological approaches to establish and validate a novel combination-based chemotherapeutic model of peripheral neuropathy. Male Sprague Dawley rats were subjected to chemotherapy administration followed by assessment of pain behaviour at different time-points post-chemotherapy. Paclit...
Source: Metabolic Brain Disease - January 1, 2024 Category: Neurology Source Type: research
Understanding the multifaceted role of miRNAs in Alzheimer ’s disease pathology
AbstractSmall non-coding RNAs (miRNAs) regulate gene expression by binding to mRNA and mediating its degradation or inhibiting translation. Since miRNAs can regulate the expression of several genes, they have multiple roles to play in biological processes and human diseases. The majority of miRNAs are known to be expressed in the brain and are involved in synaptic functions, thus marking their presence and role in major neurodegenerative disorders, including Alzheimer ’s disease (AD). In AD, amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) are known to be the major hallmarks. The clearance of Aβ and tau is ...
Source: Metabolic Brain Disease - January 1, 2024 Category: Neurology Source Type: research
Classical Hereditary galactosemia: findings in patients and animal models
AbstractClassic galactosemia is a rare inborn error of metabolism that affects the metabolism of galactose, a sugar derived from milk and derivates. Classic galactosemia is caused by variants of theGALT gene, which lead to absent or misfolded forms of the ubiquitously present galactose-1-phosphate uridylyltransferase enzyme (GALT) driving galactose metabolites to accumulate, damaging cells from neurons to hepatocytes. The disease has different prevalence around the world due to different allele frequencies among populations and its symptoms range from cognitive and psychomotor impairment to hepatic, ophthalmological, and b...
Source: Metabolic Brain Disease - January 1, 2024 Category: Neurology Source Type: research
Network pharmacology-based approach to understand the effect and mechanism of chrysophanol against cognitive impairment in Wilson disease
AbstractWilson disease (WD) is a rare hereditary copper metabolism disorder, wherein cognitive impairment is a common clinical symptom. Chrysophanol (CHR) is an active compound with neuroprotective effects. The study aims to investigate the neuroprotective effect of CHR in WD and attempted to understand the potential mechanisms. Network pharmacology analysis was applied to predict the core target genes of CHR against cognitive impairment in WD. The rats fed with copper-laden diet for 12 weeks, and the effect of CHR on the copper content in liver and 24-h urine, the learning and memory ability, the morphological changes a...
Source: Metabolic Brain Disease - January 1, 2024 Category: Neurology Source Type: research
Potential novel mechanism of selenium on cognition
(Source: Metabolic Brain Disease)
Source: Metabolic Brain Disease - January 1, 2024 Category: Neurology Source Type: research
Shark fish oil prevents scopolamine-induced memory impairment in an experimental model
AbstractFish oil has been known for its antioxidant, cardioprotective, anti-inflammatory, and neuroprotective characteristics due to the presence of polyunsaturated fatty acids (PUFAs) that are essential for optimal brain function and mental health. The present study investigated the effect of Carcharhinus Bleekeri (Shark Fish) oil on learning and memory functions in scopolamine-induced amnesia in rats. Locomotor and memory-enhancing activity in scopolamine-induced amnesic rats was investigated by assessing the open field and passive avoidance paradigm. Forty male Albino mice were divided into 4 equal groups (n = 10) a...
Source: Metabolic Brain Disease - January 1, 2024 Category: Neurology Source Type: research
Plasma metabolomics reveals the intervention mechanism of different types of exercise on chronic unpredictable mild stress-induced depression rat model
This study provides a powerful analytical tool to study the mechanism of the antidepressant effect of exercise, and provides an important method and basis for the early diagnosis, prevention and treatment of depression. (Source: Metabolic Brain Disease)
Source: Metabolic Brain Disease - January 1, 2024 Category: Neurology Source Type: research
Combination chemotherapy in rodents: a model for chemotherapy-induced neuropathic pain and pharmacological screening
AbstractChemotherapy-induced neuropathic pain (CINP) remains a therapeutic challenge, with no US-FDA approved drugs or effective treatments available. Despite significant progress in unravelling the pathophysiology of CINP, the clinical translation of this knowledge into tangible outcome remains elusive. Here, we employed behavioural and pharmacological approaches to establish and validate a novel combination-based chemotherapeutic model of peripheral neuropathy. Male Sprague Dawley rats were subjected to chemotherapy administration followed by assessment of pain behaviour at different time-points post-chemotherapy. Paclit...
Source: Metabolic Brain Disease - January 1, 2024 Category: Neurology Source Type: research
Understanding the multifaceted role of miRNAs in Alzheimer ’s disease pathology
AbstractSmall non-coding RNAs (miRNAs) regulate gene expression by binding to mRNA and mediating its degradation or inhibiting translation. Since miRNAs can regulate the expression of several genes, they have multiple roles to play in biological processes and human diseases. The majority of miRNAs are known to be expressed in the brain and are involved in synaptic functions, thus marking their presence and role in major neurodegenerative disorders, including Alzheimer ’s disease (AD). In AD, amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) are known to be the major hallmarks. The clearance of Aβ and tau is ...
Source: Metabolic Brain Disease - January 1, 2024 Category: Neurology Source Type: research
