Wnt/β-catenin (WβC) signaling pathway is an important signaling pathway for the maintenance of cellular homeostasis from the embryonic developmental stages to adulthood. The canonical pathway of WβC signaling is essential for neurogenesis, cell proliferation, and neurogenesis, whereas the noncanonical pathway (WNT/Ca2+ and WNT/PCP) is responsible for cell polarity, calcium maintenance, and cell migration. Abnormal regulation of WβC signaling is involved in the pathogenesis of several neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and spinal muscular atrophy (SMA). Hence, the alteration of WβC signaling is considered a potential therapeutic target for the treatment of neurodegenerative disease. In the present review, we have used the bibliographical information from PubMed, Google Scholar, and Scopus to address the current prospects of WβC signaling role in the abovementioned neurodegenerative diseases.
Nanoparticles (NPs) apart from their widespread advantages and increased utilisation, have aroused concerns over their safe use. Nickel (II) oxides (NiO) NPs are used as catalysts, biosensors and in many of the consumer products. The increasing use of NiO NPs necessitates an improved understanding of their potential impact on the environment and human health. In this study, we investigated the acute genotoxic effects of NiO NPs by oral route administration with three different doses (125, 250 and 500 mg/kg bw). Before the in vivo toxicological evaluation, characterisation of particles by Transmission Electron Microscopy, X-ray diffraction, Dynamic Light Scattering (DLS) and Laser Doppler Velocimetry analysis was performed. Genotoxicity biomarkers such as comet, micronucleus and chromosomal aberrations (CAs) assays were utilised in this study. To document the uptake, retention and elimination of the NPs, biodistribution studies were also performed. The particle size obtained from Transmission Electron Microscopy analysis for NiO NPs was 15.62 ± 2.59 nm. The mean hydrodynamic diameter and PdI of NiO NPs in Milli-Q water suspension obtained by DLS was 168.9 ± 17.13 nm and 0.375, respectively. Comet assay revealed significant (P < 0.001) DNA damage at 500 mg/kg bw dose in the PBL, liver and kidney cells of rats at the 24-h sampling time. The result of micronucleus and CAs tests was in agreement with the comet assay data. Biodistribution of NiO NPs revealed a maximum accumulation of Ni in the liver tissue at the 24-h sampling time. Our study showed significant DNA damage at the high dose level and the effect was more prominent at 24-h sampling time, providing preliminary evidence that the NiO NPs are capable of inducing genotoxicity when administered through the oral route. However, mechanistic investigations are needed before drawing any firm conclusion regarding the toxicology of NiO NPs.
Nickel oxide (NiO) nanoparticles (NPs) with appropriate surface chemistry have been widely used for their potential new applications in biomedical industry. Increased usage of these NPs enhances the chance of exposure of personnel involved in the work place. This study was designed to assess the ability of NiO NPs to cause biochemical alterations post-acute oral exposure in female Wistar rats. Rats were administered with 125, 250, and 500 mg/kg doses of NiO NPs for haematological, biochemical, and histopathological studies. Biodistribution patterns of NiO NPs in female Wistar rats were also monitored. NiO NPs caused significant (p < 0.01) inhibition of RBC and brain AchE of treated rats at the high dose. Activation of the hepatotoxicity marker enzymes, aminotransferases, was recorded in serum and liver, whereas inhibition was observed in kidney. The activity of antioxidant enzymes was also altered by NiO NPs in a dose-dependent manner and found to be significant at the high dose of exposure. This study revealed that exposure to nanosized NiO particles at acute doses may cause adverse changes in animal biochemical profiles. Further, the in vivo studies on toxicity evaluation help in biomonitoring of the potential contaminants.