PUMILIO competes with AUF1 to control DICER1 RNA levels and miRNA processing.

DICER1 syndrome is a cancer pre-disposition disorder caused by mutations that disrupt the function of DICER1 in miRNA processing. Studying the molecular, cellular and oncogenic effects of these mutations can reveal novel mechanisms that control cell homeostasis and tumor biology. Here, we conduct the first analysis of pathogenic DICER1 syndrome allele from the DICER1 3'UTR. We find that the DICER1 syndrome allele, rs1252940486, abolishes interaction with the PUMILIO RNA binding protein with the DICER1 3'UTR, resulting in the degradation of the DICER1 mRNA by AUF1. This single mutational event leads to diminished DICER1 mRNA and protein levels, and widespread reprogramming of miRNA networks. The in-depth characterization of the rs1252940486 DICER1 allele, reveals important post-transcriptional regulatory events that control DICER1 levels.

Toward Verification of DAG-Based Distributed Ledger Technologies through Discrete-Event Simulation.

As the potential of directed acyclic graph (DAG)-based distributed ledgers in IoT systems unfolds, a need arises to understand their intricate dynamics in real-world scenarios. It is well known that discrete event simulations can provide high-fidelity evaluations of protocols. However, there is a lack of public discrete event simulators capable of assessing DAG-based distributed ledgers. In this paper, a discrete-event-based distributed ledger simulator is introduced, with which we investigate a custom Python-based implementation of IOTA's Tangle DAG protocol. The study reveals the dynamics of Tangle (particularly Poisson processes in transaction dynamics), the efficiency and intricacies of the random walk in Tangle, and the quantitative assessment of node convergence. Furthermore, the research underscores the significance of weight updates without depth limitations and provides insights into the role, challenges, and implications of the coordinator/validator in DAG architectures. The results are striking, and although the findings are reported only for Tangle, they demonstrate the need for adaptable and versatile discrete event simulators for DAG architectures and tip selection methodologies in general.

Sequence-dependent recruitment of SRSF1 and SRSF7 to intronless lncRNA NKILA promotes nuclear export via the TREX/TAP pathway.

The TREX-TAP pathway is vital for mRNA export. For spliced mRNA, the TREX complex is recruited during splicing; however, for intronless mRNA, recruitment is sequence dependent. However, the export of cytoplasmic long noncoding RNA (lncRNA) is poorly characterized. We report the identification of a cytoplasmic accumulation region (CAR-N) in the intronless lncRNA, NKILA. CAR-N removal led to strong nuclear retention of NKILA, and CAR-N insertion promoted the export of cDNA transcripts. In vitro RNP purification via CAR-N, mass spectrometry, and siRNA screening revealed that SRSF1 and SRSF7 were vital to NKILA export, and identified a cluster of SRSF1/7 binding sites within a 55 nucleotide sequence in CAR-N. Significant nuclear enrichment of NKILA was observed for NKILA lacking CAR-N or the cluster of binding sites in knock-in models. Depletion of TREX-TAP pathway components resulted in strong nuclear retention of NKILA. RNA and protein immunoprecipitation verified that SRSF1/7 were bound to NKILA and interacted with UAP56 and ALYREF. Moreover, NKILA lacking CAR-N was unable to inhibit breast cancer cell migration. We concluded that the binding of SRSF1/7 to clustered motifs in CAR-N facilitated TREX recruitment, promoting the export of NKILA, and confirmed the importance of NKILA localization to its function.

The efficacy of therapist-supported acceptance and commitment therapy-based bibliotherapy for psychological distress after stroke: a single-case multiple-baseline study.

BACKGROUND: Psychological distress is common after stroke, and affects recovery. However, there are few evidence-based psychological treatments. This study evaluates a bibliotherapy-based approach to its amelioration. AIMS: To investigate a stroke-specific self-management book, based on acceptance and commitment therapy (ACT), as a therapist-supported intervention for psychological distress after stroke. METHOD: The design was a single case, randomised non-concurrent multiple-baseline design (MBD). Sixteen stroke survivors, eight males and eight females (mean age 60.6 years), participated in an MBD with three phases: A (randomised-duration baseline); B (intervention); and follow-up (at 3 weeks). During the baseline, participants received therapist contact only. In the bibliotherapy intervention, participants received bi-weekly therapist support. The primary measures of psychological distress (General Health Questionaire-12; GHQ-12) and quality of life (Satisfaction with Life Scale; SWLS) were completed weekly. Secondary measures of mood, wellbeing and illness impact were completed pre- and post-intervention. RESULTS: Omnibus whole-group TAU-U analysis was statistically significant for each primary measure with a moderate effect size on both (0.6 and 0.3 for GHQ-12 and SWLS, respectively). Individual TAU-U analyses demonstrated that the majority of individuals exhibited positive change. All the secondary measures showed significant pre-post improvements. Eighty-one per cent of participants reported the book was helpful and 81% also found the ACT-based sections helpful. Relative risk calculations showed finding the book helpful was associated with improvement in GHQ-12 and SWLS scores. CONCLUSIONS: ACT-based bibliotherapy, with therapist support, is a promising intervention for psychological difficulties after stroke.

A Survey and Ontology of Blockchain Consensus Algorithms for Resource-Constrained IoT Systems.

The basic properties of blockchain, such as decentralization, security, and immutability, show promising potential for IoT applications. The main feature-decentralization of blockchain technology-depends on the consensus. However, consensus algorithms are mostly designed to work in extensive computational and communication environments for network security and immutability, which is not desirable for resource-restricted IoT applications. Many solutions are proposed to address this issue with modified consensus algorithms based on the legacy consensus, such as the PoW, PoS, and BFT, and new non-linear data structures, such as DAG. A systematic classification and analysis of various techniques in the field will be beneficial for both researchers and industrial practitioners. Most existing relevant surveys provide classifications intuitively based on the domain knowledge, which are infeasible to reveal the intrinsic and complicated relationships among the relevant basic concepts and techniques. In this paper, a powerful tool of systematic knowledge classification and explanation is introduced to structure the survey on blockchain consensus algorithms for resource-constrained IoT systems. More specifically, an ontology was developed for a consensus algorithm apropos of IoT adaptability. The developed ontology is subdivided into two parts-CONB and CONIoT-representing the classification of generic consensus algorithms and the ones that are particularly proposed for IoT, respectively. Guided by this ontology, an in depth discussion and analysis are provided on the major consensus algorithms and their IoT compliance based on design and implementation targets. Open research challenges and future research directions are provided.

XAB2 depletion induces intron retention in POLR2A to impair global transcription and promote cellular senescence.

XAB2 is a multi-functional protein participating processes including transcription, splicing, DNA repair and mRNA export. Here, we report POLR2A, the largest catalytic subunit of RNA polymerase II, as a major target gene down-regulated after XAB2 depletion. XAB2 depletion led to severe splicing defects of POLR2A with significant intron retention. Such defects resulted in substantial loss of POLR2A at RNA and protein levels, which further impaired global transcription. Treatment of splicing inhibitor madrasin induced similar reduction of POLR2A. Screen using TMT-based quantitative proteomics identified several proteins involved in mRNA surveillance including Dom34 with elevated expression. Inhibition of translation or depletion of Dom34 rescued the expression of POLR2A by stabilizing its mRNA. Immuno-precipitation further confirmed that XAB2 associated with spliceosome components important to POLR2A expression. Domain mapping revealed that TPR motifs 2-4 and 11 of XAB2 were critical for POLR2A expression by interacting with SNW1. Finally, we showed POLR2A mediated cell senescence caused by XAB2 deficiency. Depletion of XAB2 or POLR2A induced cell senescence by up-regulation of p53 and p21, re-expression of POLR2A after XAB2 depletion alleviated cellular senescence. These data together support that XAB2 serves as a guardian of POLR2A expression to ensure global gene expression and antagonize cell senescence.

Nuclear retention element recruits U1 snRNP components to restrain spliced lncRNAs in the nucleus.

In contrast to cytoplasmic localization of spliced mRNAs, many spliced lncRNAs are localized in the nucleus. To investigate the mechanism, we used lncRNA MEG3 as a reporter and mapped a potent nuclear retention element (NRE), deletion of this element led to striking export of MEG3 from the nucleus to the cytoplasm. Insertion of the NRE resulted in nuclear retention of spliced lncRNA as well as spliced mRNA. We further purified RNP assembled on the NRE in vitro and identified the proteins by mass spectrometry. Screen using siRNA revealed depletion of U1 snRNP components SNRPA, SNRNP70 or SNRPD2 caused significant cytoplasmic localization of MEG3 reporter transcripts. Co-knockdown these factors in HFF1 cells resulted in an increased cytoplasmic distribution of endogenous lncRNAs. Together, these data support a model that U1 snRNP components restrain spliced lncRNAs in the nucleus via the interaction with nuclear retention element.

Complications of Cryolipolysis: Paradoxical Adipose Hyperplasia (PAH) and Beyond.

BACKGROUND: Cryolipolysis is a fairly popular procedure performed in North America, Europe, and many other countries. Although it is considered a rather safe procedure, there are underreported side effects such as paradoxical adipose hyperplasia (PAH), contour irregularities, skin and soft tissue atrophy, and asymmetries. Our knowledge regarding the prevalence and treatment of such complications is limited. OBJECTIVES: We hereby report a case series of 5 patients treated for various complications of cryolipolysis, including PAH, that persisted for more than 12 months after their last treatment. METHODS: Five patients with various complications of cryolipolysis (4 patients with PAH and 1 with atrophy and indentations) presented in our private office between 2015 and 2018. Three of the 4 patients with PAH were treated at other facilities with ultrasonic liposuction, laser lipolysis, and radiofrequency skin tightening devices respectively. The fourth patient developed PAH after liposuction at another facility. The fifth patient developed several areas of indentations and atrophy and received mesotherapy and lymphatic massages at another facility. All 5 patients were subsequently treated in our office by means of a customized approach specific to their underlying complications. RESULTS: Near-normal results were achieved in all 5 patients. None of our patients showed any recurrences of their initial complication for which they were treated. All 5 patients were extremely satisfied with their results. CONCLUSIONS: Cryolipolysis, just like any other form of lipolysis, has certain specific adverse effects associated with it, including but not limited to PAH. Complications of cryolipolysis must be individually recognized and treated accordingly.

Risk factors and patterns of recurrence after curative resection in Gastroesophageal Junction Adenocarcinoma.

OBJECTIVES: We looked at risk factors and patterns of recurrence following surgical treatment of Gastro-Oesophageal Junction carcinoma (GOJC). METHODS: Electronic medical records of patients with GOJC undergoing resection with curative intent between Jan 2009 and June 2017 at Shaukat Khanum Memorial Cancer Hospital were reviewed. GOJ cancer was classified as per Siewert classification. Clinical and operative details were studied and data was analysed using SPSS 20. RESULTS: During the study period, we identified 78 patients with GOJ adenocarcinoma (38 patients with GOJ Type-I, 16 with Type-II tumors and 24 patients with GOJ Type-III tumors). Median age was 56 years ± 1.1. Male to female distribution was 72 versus 28%. Carbo-Pacli /5-FU based XRT verses Magic protocol (p<0.015) and advanced pathological T.-stage (p-value<0.032) were found to be statistically significant risk factors for recurrence. After a median follow up of 17.8 months+/- 1.5, 20 patients developed recurrence of which five had local recurrence, three had regional recurrence, eight had distant metastases and four had both local and distant metastases. CONCLUSION: The incidence of recurrence following curative resection of GOJC is 25%. Type of neoadjuvant treatment, waiting time for surgery and advanced T-stage are a risk factor for recurrence.

Designing Novel Nonsymmetric Ag/AgI Nanoplates for Superior Photocatalytic Activity.

Precisely engineering the decoration of metal nanoparticles on the special surface of semiconductor represents a promising strategy to design efficient metal-semiconductor heterostructured photocatalysts. This study demonstrates a versatile soft-template method to fabricate a novel nonsymmetrical heterostructured Ag/AgI nanoplate, in which only one side surface of the nanoplate is covered with uniform 2D Ag nanoweb. Compared with symmetrical heterostructure, the nonsymmetrical heterostructure may further facilitate the separation of photogenerated electron-hole pairs and shows a greatly enhanced photocatalytic activity. This study may open up a new way to improve the photocatalytic property by synthesizing nonsymmetrical metal-semiconductor composites.

Microwave and conventional synthesis of Co (II), Cu (II) and Ni (II) metal complexes of some acid hydrazones with their spectral characterization and biological evaluation.

The transition metal complexes of Co(II), Ni(II), and Cu(II) derived from N'-((5-(2,5-dichlorophenyl)furan-2-yl)methylene)-2-hydroxybenzohydrazide (L24) and N'-((5-(2, 5-dichlorophenyl)furan-2-yl)methylene)benzohydrazide (L21) have been synthesized by conventional as well as microwave method being shorter time consuming, solvent less and gives improved yields as compared to the traditional conventional technique. These compounds were characterized by melting point, TLC, FTIR, 1H-NMR, elemental analysis, potentiometric titration, ICP-OES and EIMS. From this analytical data it is confirmed that complexes are in octahedral structure with coordination number 6 which revealed 1:2 (metal:ligand). FTIR data shows that these synthesized hydrazone ligands have ONO donor sites and coordinate with transition metal ions in a tridentate monobasic manner. All these synthesized compounds were tested for evaluation of antibacterial activity by agar disc diffusion assay and total antioxidant activity by Phosphomolybdenum method.

Morbidity analysis in minimally invasive esophagectomy for oesophageal cancer versus conventional over the last 10 years, a single institution experience.

BACKGROUND: There has been an increasing inclination towards minimally invasive esophagectomies (MIEs) at our institute recently for resectable oesophageal cancer. OBJECTIVES: The purpose of the present study is to report peri-operative and long-term procedure specific outcomes of the two groups and analyse their changing pattern at our institute. METHODS: All adult patients with a diagnosis of oesophageal cancer managed at our institute from 2005 to 2015 were included in this retrospective study. Patients' demographic and clinical characteristics were recorded through our hospital information system. The cohort of esophagectomies was allocated into two groups, conventional open esophagectomy (OE) or total laparoscopic MIE; hybrid esophagectomies were taken as a separate group. The short-term outcome measures are an operative time in minutes, length of hospital and Intensive Care Unit (ICU) stay in days, post-operative complications and 30 days in-hospital mortality. Complications are graded according to the Clavien-Dindo classification system. Long-term outcomes are long-term procedure related complications over a minimum follow-up of 1 year. Trends were analysed by visually inspecting the graphic plots for mean number of events in each group each year. RESULTS: Our results showed no difference in mortality, length of hospital and ICU stays and incidence of major complications between three groups on uni- and multi-variate analysis (P > 0.05). The operative time was significantly longer in MIE group (odds ratio [OR]: 1.66, confidence interval [CI]: 2.4-11.5). The incidence of long-term complication was low for MIE (OR: 1.0, CI: 133-1.017). However, all post-operative surgical outcomes trended to improve in both groups over the course of this study and stayed better for MIE group except for the operative time. CONCLUSION: MIE has overall comparable surgical outcomes to its conventional counterpart. Furthermore, the peri-operative outcomes tend to improve in our centre with the maturation of program and experience.

Role of C-reactive protein as a marker for microalbuminuria in type 2 diabetics.

BACKGROUND: One of the most important complications of Type 2 diabetes mellitus is diabetic nephropathy which is reported as the leading cause of premature deaths due to renal failure. This study was being conducted to see the role of C-reactive protein a marker in type 2 diabetic patient with micro-albuminuria. METHODS: This cross sectional study was carried out in the Diabetic Clinic of Pakistan Medical Research Council, Research Centre Lahore. Personal history about the disease was collected on a questionnaire. Blood and urine sample of 50 type 2 diabetic patients between the ages of 40-65 years were collected to analyze C-reactive protein and micro-albuminuria respectively. Data were analyzed using SPSS-15. The Pearson correlation coefficient test was used to determine correlation between urine albumin and C-reactive protein. RESULTS: There were 22 micro- albuminuria positive cases out of total 50 diabetic cases. Of these 14 (63%) showed raised C-reactive protein levels (p < 0.00). CONCLUSION: There is significant association between the level of serum C- reactive proteins and micro-albuminuria in type 2 diabetics.

A machine learning driven automated system for safety data sheet indexing.

Safety Data Sheets (SDS) are foundational to chemical management systems and are used in a wide variety of applications such as green chemistry, industrial hygiene, and regulatory compliance, among others within the Environment, Health, and Safety (EHS) and the Environment, Social, and Governance (ESG) domains. Companies usually prefer to have key pieces of information extracted from these datasheets and stored in an easy to access structured repository. This process is referred to as SDS "indexing". Historically, SDS indexing has always been done manually, which is labor-intensive, time-consuming, and costly. In this paper, we present an automated system to index the composition information of chemical products from SDS documents using a multi-stage ensemble method with a combination of machine learning models and rule-based systems stacked one after the other. The system specifically indexes the ingredient names, their corresponding Chemical Abstracts Service (CAS) numbers, and weight percentages. It takes the SDS document in PDF format as the input and gives the list of ingredient names along with their corresponding CAS numbers and weight percentages in a tabular format as the output. The system achieves a precision of 0.93 at the document level when evaluated on 20,000 SDS documents annotated for this purpose.

Initial local resection versus early referral for spermatic cord sarcoma: Any impact on treatment timelines and oncological outcomes?

OBJECTIVES: Spermatic cord sarcomas are exceedingly rare, often misdiagnosed and subsequently improperly treated at local hospitals. This retrospective study looked at the oncological outcomes of spermatic cord sarcoma cases managed with curative intent resection at a tertiary referral sarcoma centre. We specifically studied how initial inadequate resections impact the oncologic outcomes compared to primary tumour resections at the reference centre. METHODS: One hundred eighteen consecutive patients affected by primary, localized spermatic cord sarcoma surgically managed at our reference centre from January 2001 through January 2021 were included. Primary endpoints were local relapse free (LRFS), distant metastasis free (DMFS) and overall survival (OS). These outcomes were evaluated with multi-nomial logistic regression and Cox proportional hazards regression models for a co-relation to known patient, tumour and treatment-related prognostic factors, including a prior inadequate resection and time from diagnosis to a complete oncologic resection as independent variables. Secondarily, we compared the above variables and treatment intervals among the subgroups of primary versus re-resection surgery. RESULTS: Over a median follow-up of 54 months (IQR 25-105), 12 patients (10.2%) developed local recurrence (LR) and 14 (11.6%) had distant metastasis (DM). 5-year local relapse (LRFS) and distant metastasis-free survival (DMFS) were 89.3% and 86.5%, respectively. Higher tumour grade and size were associated with a worse DMFS (p=<0.05). Likewise, marginal (R1) resection correlated with an inferior LRFS (p=< 0.05). Eighty-four patients (71.2%) had their initial diagnosis established on an inadequate surgical excision performed in a local hospital, followed by a re-excision at our centre (Re-resection group). During the same period, 34 (28.8%) were managed primarily with biopsy and treatment at our reference centre (Primary-resection group). The two groups had statistically significant differences in tumour size, histopathology, surgery duration, rate of postoperative complication and R0 resection (p < 0.005). Additionally, the difference in time intervals to achieve the treatment targets was statistically insignificant and did not correlate to the risk of recurrence as an independent variable. Residual disease was present in 51.2 % (n = 43) of the re-excision specimens. However, following a complete R0 resection, this did not correlate with a higher risk of recurrence (p = 0.481). CONCLUSION: Prompt referral to a tertiary centre, where multidisciplinary evaluation and sound oncologic resections are the standard of treatment, can align the OS and DFS of patients receiving incomplete surgery elsewhere to those treated primarily in referral centres. The primary determinant of prognosis remains surgical margin, tumour size and grade.

Intrinsic Room-Temperature Ferromagnetism in New Halide Perovskite AgCrX3 (X: F, Cl, Br, I) Using Ab Initio and Monte Carlo Simulations.

Herein, we present a detailed comparative study of the structural, elastic, electronic, and magnetic properties of a series of new halide perovskite AgCrX3 (X: F, Cl, Br, I) crystal structures using density functional theory, mean-field theory (MFT), and quantum Monte Carlo (MC) simulations. As demonstrated by the negative formation energy and Born-Huang stability criteria, the suggested perovskite compounds show potential stability in the cubic crystal structure. The materials are ductile because the Pugh's ratio is greater than 1.75, and the Cauchy pressure (C12-C44) is positive. The ground state magnetic moments of the compound were calculated as 3.70, 3.91, 3.92, and 3.91 µB for AgCrF3, AgCrCl3, AgCrBr3, and AgCrI3, respectively. The GGA + SOC computed spin-polarized electronic structures reveal ferromagnetism and confirm the metallic character in all of these compounds under consideration. These characteristics are robust under a ±3% strained lattice constant. Using relativistic pseudopotentials, the total energy is calculated, which yields that the single ion anisotropy is 0.004 meV and the z-axis is the hard-axis in the series of AgCrX3 (X: F, Cl, Br, and I) compounds. Further, to explore room-temperature intrinsic ferromagnetism, we considered ferromagnetic and antiferromagnetic interactions of the magnetic ions in the compounds by considering a supercell with 2 × 2 × 2 dimensions. The transition temperature is estimated by two models, namely, MFT and MC simulations. The calculated Curie temperatures using MC simulations are 518.35, 624.30, 517.94, and 497.28 K, with ±5% error for AgCrF3, AgCrCl3, AgCrBr3, and AgCrI3 compounds, respectively. Our results suggest that halide perovskite AgCrX3 compounds are promising materials for spintronic nanodevices at room temperature and provide new recommendations. For the first time, we report results for novel halide perovskite compounds based on Ag and Cr atoms.

Synthesis, In Vitro Biological Evaluation and Molecular Modeling of Benzimidazole-Based Pyrrole/Piperidine Hybrids Derivatives as Potential Anti-Alzheimer Agents.

Benzimidazole-based pyrrole/piperidine analogs (1-26) were synthesized and then screened for their acetylcholinesterase and butyrylcholinesterase activities. All the analogs showed good to moderate cholinesterase activities. Synthesized compounds (1-13) were screened in cholinesterase enzyme inhibition assays and showed AChE activities in the range of IC50 = 19.44 ± 0.60 µM to 36.05 ± 0.4 µM against allanzanthane (IC50 = 16.11 ± 0.33 µM) and galantamine (IC50 = 19.34 ± 0.62 µM) and varied BuChE inhibitory activities, with IC50 values in the range of 21.57 ± 0.61 µM to 39.55 ± 0.03 µM as compared with standard allanzanthane (IC50 = 18.14 ± 0.05 µM) and galantamine (IC50 = 21.45 ± 0.21 µM). Similarly, synthesized compounds (14-26) were also subjected to tests to determine their in vitro AChE inhibitory activities, and the results obtained corroborated that all the compounds showed varied activities in the range of IC50 = 22.07 ± 0.13 to 42.01 ± 0.02 µM as compared to allanzanthane (IC50 = 20.01 ± 0.12 µM) and galantamine (IC50 = 18.05 ± 0.31 µM) and varied BuChE inhibitory activities, with IC50 values in the range of 26.32 ± 0.13 to 47.03 ± 0.15 µM as compared to standard allanzanthane (IC50 = 18.14 ± 0.05 µM) and galantamine (IC50 = 21.45 ± 0.21 µM). Binding interactions of the most potent analogs were confirmed through molecular docking studies. The active analogs 2, 4, 10 and 13 established numerous interactions with the active sites of targeted enzymes, with docking scores of -10.50, -9.3, -7.73 and -7.8 for AChE and -8.97, -8.2, -8.20 and -7.6 for BuChE, respectively.

Mechanisms of RNA export and nuclear retention.

With the identification of huge amount of noncoding RNAs in recent years, the concept of RNA localization has extended from traditional mRNA export to RNA export of mRNA and ncRNA as well as nuclear retention of ncRNA. This review aims to summarize the recent findings from studies on the mechanisms of export of different RNAs and nuclear retention of some lncRNAs in higher eukaryotes, with a focus on splicing-dependent TREX recruitment for the export of spliced mRNA and the sequence-dependent mechanism of mRNA export in the absence of splicing. In addition, evidence to support the involvement of m6 A modification in RNA export with the coordination between the methylase complex and TREX complex as well as sequence-dependent nuclear retention of lncRNA is recapitulated. Finally, a model of sequence-dependent RNA localization is proposed along with the many questions that remain to be answered. This article is categorized under: RNA Export and Localization > RNA Localization RNA Export and Localization > Nuclear Export/Import.

The Molecular Basis of Wnt/ß-Catenin Signaling Pathways in Neurodegenerative Diseases.

Defective Wnt signaling is found to be associated with various neurodegenerative diseases. In the canonical pathway, the Frizzled receptor (Fzd) and the lipoprotein receptor-related proteins 5/6 (LRP5/LRP6) create a seven-pass transmembrane receptor complex to which the Wnt ligands bind. This interaction causes the tumor suppressor adenomatous polyposis coli gene product (APC), casein kinase 1 (CK1), and GSK-3ß (glycogen synthase kinase-3 beta) to be recruited by the scaffold protein Dishevelled (Dvl), which in turn deactivates the ß-catenin destruction complex. This inactivation stops the destruction complex from phosphorylating ß-catenin. As a result, ß-catenin first builds up in the cytoplasm and then migrates into the nucleus, where it binds to the Lef/Tcf transcription factor to activate the transcription of more than 50 Wnt target genes, including those involved in cell growth, survival, differentiation, neurogenesis, and inflammation. The treatments that are currently available for neurodegenerative illnesses are most commonly not curative in nature but are only symptomatic. According to all available research, restoring Wnt/ß-catenin signaling in the brains of patients with neurodegenerative disorders, particularly Alzheimer's and Parkinson's disease, would improve the condition of several patients with neurological disorders. The importance of Wnt activators and modulators in patients with such illnesses is to mainly restore rather than overstimulate the Wnt/ß-catenin signaling, thereby reestablishing the equilibrium between Wnt-OFF and Wnt-ON states. In this review, we have tried to summarize the significance of the Wnt canonical pathway in the pathophysiology of certain neurodegenerative diseases, such as Alzheimer's disease, cerebral ischemia, Parkinson's disease, Huntington's disease, multiple sclerosis, and other similar diseases, and as to how can it be restored in these patients.