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.

Acquiring the recommended daily allowance of vitamins is crucial for maintaining homeostatic balance in humans and other animals. A deficiency in or dysregulation of vitamins adversely affects the neuronal metabolism, which may lead to neurodegenerative diseases. In this article, we discuss how novel vitamin-based approaches aid in attenuating abnormal neuronal functioning in neurodegeneration-based brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, and Prion disease. Vitamins show their therapeutic activity in Parkinson’s disease by antioxidative and anti-inflammatory activity. In addition, different water- and lipid-soluble vitamins have also prevented amyloid beta and tau pathology. On the other hand, some results also show no correlation between vitamin action and the prevention of neurodegenerative diseases. Some vitamins also exhibit toxic activity too. This review discusses both the beneficial and null effects of vitamin supplementation for neurological disorders. The detailed mechanism of action of both water- and lipid-soluble vitamins is addressed in the manuscript. Hormesis is also an essential factor that is very helpful to determine the effective dose of vitamins. PubMed, Google Scholar, Web of Science, and Scopus were employed to conduct the literature search of original articles, review articles, and meta-analyses.

Neurodegenerative diseases (NDs) represent a common neurological pathology that determines a progressive deterioration of the brain or the nervous system. For treating NDs, comprehensive and alternative medicines have attracted scientific researchers' attention recently. Edible mushrooms are essential for preventing several age-based neuronal dysfunctions such as Parkinson's and Alzheimer's diseases. Mushroom such as Grifola frondosa, Lignosus rhinocerotis, Hericium erinaceus, may improve cognitive functions. It has also been reported that edible mushrooms (basidiocarps/mycelia extracts or isolated bioactive compounds) may reduce beta-amyloid-induced neurotoxicity. Medicinal mushrooms are being used for novel and natural compounds that help modulate immune responses and possess anti-cancer, anti-microbial, and anti-oxidant properties. Compounds such as polyphenols, terpenoids, alkaloids, sesquiterpenes, polysaccharides, and metal chelating agents are validated in different ND treatments. This review aims to assess mushrooms' role and their biomolecules utilization for treating different kinds of NDs. The action mechanisms, presented here, including reducing oxidative stress, neuroinflammation, and modulation of acetylcholinesterase activity, protecting neurons or stimulation, and regulating neurotrophins synthesis. We also provide background about neurodegenerative diseases and in-silico techniques of the drug research. High costs associated with experiments and current ethical law imply efficient alternatives with limited cost value. In silico approaches provide an alternative method with low cost that has been successfully implemented to cure ND disorders in recent days. We also describe the applications of computational procedures such as molecular docking, virtual high-throughput screening, molecular dynamic (MD) simulation, quantum-mechanical methods for drug design. They were reported against various targets in NDs.

Introduction: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, surpassed only by Alzheimer's disease. It is distinguished by a diverse array of motor and non-motor symptoms that impact various aspects of neurological function. In recent years, the autophagy-enhancing potential of several medicinal plants has been tested and results in better protection against neurodegeneration in PD. Accordingly, the major objective of this work is to explore the autophagy-enhancing activity of Mucuna pruriens (Mp) seed extract in the rotenone intoxicated mouse model. Method: To evaluate our hypothesis, we categorized the mice into four distinct groups: a control group, a drug-only control group, a rotenone-intoxicated group, and a group of rotenone-intoxicated mice that were also treated with Mp. After dosing was finished, the behavioral test was measured. The mice were then sacrificed in each group, and the brains were isolated. Rotenone-intoxicated Parkinsonian mice exhibited significant behavioral impairments in the rotarod, hanging grip, and narrow beam walking tests, indicating deficits in balance, coordination, and muscle strength. Treatment with Mp markedly improved motor performance, suggesting its neuroprotective and therapeutic potential in alleviating PD-related dysfunction. Similarly, Mp effectively mitigates biochemical impairments in the Parkinsonian mouse model, improving catalase activity, reducing nitrite levels, lipid peroxidation, and enhancing glutathione reductase function. TFEB and mTORC1 are the 2 most important modulators of autophagy. The TFEB level was decreases in the rotenone group ultimately restored in the Mp group. The activity of TFEB was negatively regulated by mTORC1. The level of mTORC1 was increased in rotenone group and was significantly reduced by Mp treatment. The enzymatic level of glucocerebrosidase was also decreased in rotenone intoxicated mice and increased in Mp group. The ultimate impact of these autophagy enhancers is reflected at the level of Tyrosine hydroxylase (TH). The activity of TH is reduced in the rotenone group and consequently enhanced by Mp treatment. Result: Our result shows the autophagy enhancing activity of Mp. Discussion: These findings support the potential of Mucuna pruriens as a neuroprotective agent through its ability to modulate key components of the autophagy pathway. By restoring TFEB expression and inhibiting mTORC1 activity, Mp may promote lysosomal biogenesis and autophagic clearance, processes essential for neuronal survival in PD. The upregulation of glucocerebrosidase and TH further confirms its role in maintaining dopaminergic neuron function. These outcomes highlight Mp’s multifaceted mechanism of action, suggesting its value not only as a symptomatic treatment but also as a disease-modifying agent. However, the study’s translational relevance requires further validation in clinical models. Conclusion: Further studies will be needed to search and test the additional number of regulators that are involved in the autophagy mediating activity of Mp.