Cyclin-dependent kinase 5 (CDK5) inhibitors in Parkinson disease.

Cyclin-dependent kinase 5 (Cdk5) is a protein expressed in postmitotic neurons in the central nervous system (CNS). Cdk5 is activated by p35 and p39 which are neuron regulatory subunits. Cdk5/p35 complex is activated by calpain protease to form Cdk5/p35 which has a neuroprotective effect by regulating the synaptic plasticity and memory functions. However, exaggerated Cdk5 is implicated in different types of neurodegenerative diseases including Parkinson disease (PD). Therefore, modulation of Cdk5 signalling may mitigate PD neuropathology. Therefore, the aim of the present review was to discuss the critical role of Cdk5 in the pathogenesis of PD, and how Cdk5 inhibitors are effectual in the management of PD. In conclusion, overactivated Cdk5 is involved the development of neurodegeneration, and Cdk5/calpain inhibitors such as statins, metformin, fenofibrates and rosiglitazone can attenuate the progression of PD neuropathology.

Early intervention and care for Diabetic Foot Ulcers in Low and Middle Income Countries: Addressing challenges and exploring future strategies: A narrative review.

Background and Aims: Diabetic Foot Ulcers (DFUs) are a significant health concern, particularly in Low- and Middle-Income Countries (LMICs). This review explores key strategies for managing DFUs in LMICs, including integrating podiatry, endocrinology, and wound care services, educating patients, promoting self-care, and preventive measures to reduce amputation rates. Methods: A comprehensive literature review was conducted, focusing on studies conducted in Low and Middle Income Countries to facilitate a qualitative analysis. The review examined the aetiology and risk factors to developing DFUs, clinical presentation, multidisciplinary management and evidence based interventions, challenges to the provision of care and future directions, all pertaining to DFUs in low and middle income countries. Results: The aetiology and risk factors contributing to the development of DFUs are complex and multifaceted. Factors such as limited access to health care, inadequate diabetes management, and socioeconomic disparities significantly influence the incidence of DFUs. Clinical presentation varies, with patients often presenting at advanced stages of the disease due to delayed or missed diagnoses. Multidisciplinary management, incorporating podiatry, endocrinology, and wound care services, has exhibited substantial promise in enhancing patient outcomes. Evidence-based interventions, including offloading techniques, wound debridement, and the use of advanced wound dressings, have proven effective in promoting ulcer healing. Conclusion: The burden of DFUs in LMICs requires comprehensive strategies. Integrating podiatry, endocrinology, and wound care services, along with patient education and self-care practices, is essential for reducing amputations and improving patients' quality of life. Regular follow-up and early detection are vital for effective DFU management, emphasizing the need for ongoing research and investment in LMIC health care infrastructure. Embracing these multidisciplinary, patient-centered approaches can effectively address the challenge of DFUs in LMICs, leading to better patient outcomes and improved quality of life.

BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy.

Parkinson's disease (PD) is a neurodegenerative disorder of the brain and is manifested by motor and non-motor symptoms because of degenerative changes in dopaminergic neurons of the substantia nigra. PD neuropathology is associated with mitochondrial dysfunction, oxidative damage and apoptosis. Thus, the modulation of mitochondrial dysfunction, oxidative damage and apoptosis by growth factors could be a novel boulevard in the management of PD. Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase type B (TrkB) are chiefly involved in PD neuropathology. BDNF promotes the survival of dopaminergic neurons in the substantia nigra and enhances the functional activity of striatal neurons. Deficiency of the TrkB receptor triggers degeneration of dopaminergic neurons and accumulation of α-Syn in the substantia nigra. As well, BDNF/TrkB signalling is reduced in the early phase of PD neuropathology. Targeting of BDNF/TrkB signalling by specific activators may attenuate PD neuropathology. Thus, this review aimed to discuss the potential role of BDNF/TrkB activators against PD. In conclusion, BDNF/TrkB signalling is decreased in PD and linked with disease severity and long-term complications. Activation of BDNF/TrkB by specific activators may attenuate PD neuropathology.

Natural products in the management of neurodegenerative diseases.

Neurodegenerative diseases represent one of the utmost imperative well-being health issues and apprehensions due to their escalating incidence of mortality. Natural derivatives are more efficacious in various preclinical models of neurodegenerative illnesses. These natural compounds include phytoconstituents in herbs, vegetables, fruits, nuts, and marine and freshwater flora, with remarkable efficacy in mitigating neurodegeneration and enhancing cognitive abilities in preclinical models. According to the latest research, the therapeutic activity of natural substances can be increased by adding phytoconstituents in nanocarriers such as nanoparticles, nanogels, and nanostructured lipid carriers. They can enhance the stability and specificity of the bioactive compounds to a more considerable extent. Nanotechnology can also provide targeting, enhancing their specificity to the respective site of action. In light of these findings, this article discusses the biological and therapeutic potential of natural products and their bioactive derivatives to exert neuroprotective effects and some clinical studies assessing their translational potential to treat neurodegenerative disorders.

Unraveling the Endocannabinoid System: Exploring Its Therapeutic Potential in Autism Spectrum Disorder.

The salient features of autism spectrum disorder (ASD) encompass persistent difficulties in social communication, as well as the presence of restricted and repetitive facets of behavior, hobbies, or pursuits, which are often accompanied with cognitive limitations. Over the past few decades, a sizable number of studies have been conducted to enhance our understanding of the pathophysiology of ASD. Preclinical rat models have proven to be extremely valuable in simulating and analyzing the roles of a wide range of established environmental and genetic factors. Recent research has also demonstrated the significant involvement of the endocannabinoid system (ECS) in the pathogenesis of several neuropsychiatric diseases, including ASD. In fact, the ECS has the potential to regulate a multitude of metabolic and cellular pathways associated with autism, including the immune system. Moreover, the ECS has emerged as a promising target for intervention with high predictive validity. Particularly noteworthy are resent preclinical studies in rodents, which describe the onset of ASD-like symptoms after various genetic or pharmacological interventions targeting the ECS, providing encouraging evidence for further exploration in this area.

The compelling role of allopurinol in hyperuricemia-induced epilepsy: Unrecognized like tears in rain.

Epilepsy is a common neurological disease characterized by the recurrent, paroxysmal, and unprovoked seizures. It has been shown that hyperuricemia enhances and associated with the development and progression of epilepsy through induction of inflammation and oxidative stress. In addition, uric acid is released within the brain and contributes in the development of neuronal hyperexcitability and epileptic seizure. Brain uric acid acts as damage associated molecular pattern (DAMP) activates the immune response and induce the development of neuroinflammation. Therefore, inhibition of xanthine oxidase by allopurinol may reduce hyperuricemia-induced epileptic seizure and associated oxidative stress and inflammation. However, the underlying mechanism of allopurinol in the epilepsy was not fully elucidated. Therefore, this review aims to revise from published articles the link between hyperuricemia and epilepsy, and how allopurinol inhibits the development of epileptic seizure.

Depression and type 2 diabetes: A causal relationship and mechanistic pathway.

Depression is a mood disorder that may increase risk for the development of insulin resistance (IR) and type 2 diabetes (T2D), and vice versa. However, the mechanistic pathway linking depression and T2D is not fully elucidated. The aim of this narrative review, therefore, was to discuss the possible link between depression and T2D. The coexistence of T2D and depression is twice as great compared to the occurrence of either condition independently. Hyperglycaemia and dyslipidaemia promote the incidence of depression by enhancing inflammation and reducing brain serotonin (5-hydroxytryptamine [5HT]). Dysregulation of insulin signalling in T2D impairs brain 5HT signalling, leading to the development of depression. Furthermore, depression is associated with the development of hyperglycaemia and poor glycaemic control. Psychological stress and depression promote the development of T2D. In conclusion, T2D could be a potential risk factor for the development of depression through the induction of inflammatory reactions and oxidative stress that affect brain neurotransmission. In addition, chronic stress in depression may induce the development of T2D through dysregulation of the hypothalamic-pituitary-adrenal axis and increase circulating cortisol levels, which triggers IR and T2D.

Extracellular vesicle-mediated drug delivery in breast cancer theranostics.

Breast cancer (BC) continues to be a significant global challenge due to drug resistance and severe side effects. The increasing prevalence is alarming, requiring new therapeutic approaches to address these challenges. At this point, Extracellular vesicles (EVs), specifically small endosome-released nanometer-sized EVs (SEVs) or exosomes, have been explored by literature as potential theranostics. Therefore, this review aims to highlight the therapeutic potential of exosomes in BC, focusing on their advantages in drug delivery and their ability to mitigate metastasis. Following the review, we identified exosomes' potential in combination therapies, serving as miRNA carriers and contributing to improved anti-tumor effects. This is evident in clinical trials investigating exosomes in BC, which have shown their ability to boost chemotherapy efficacy by delivering drugs like paclitaxel (PTX) and doxorubicin (DOX). However, the translation of EVs into BC therapy is hindered by various challenges. These challenges include the heterogeneity of EVs, the selection of the appropriate parent cell, the loading procedures, and determining the optimal administration routes. Despite the promising therapeutic potential of EVs, these obstacles must be addressed to realize their benefits in BC treatment.

Physicochemical Evaluation and Pharmacological Screening of Fernando Adenophylla Steenis Fruits.

The current study aimed to evaluate the physicochemical properties of Fernandoa adenophylla. Powder studies were carried out to estimate the quantitative physicochemical characteristics of the crude drug, including moisture content, ash content, and extractive values. Using a Soxhlet apparatus and different analytical grade solvents, 3 sample extracts of a crude drug were made. To evaluate the potentially toxic nature, an acute oral toxicity study was performed as per OECD guideline no. 423. Sample extracts were tested and analyzed by ANOVA for pharmacological potential (analgesic, antipyretic, and antidiabetic) using Wister-Albino rats. Where physicochemical analysis indicated purity, quality, and presence of organic/inorganic materials in crude drug extracts, no sign of mortality was found up to 2000 mg/kg of body weight of Fernandoa adenophyllas extracts. Analgesic activity was observed in all sample extracts, whereas only chloroform and ethanolic extracts expressed antipyretic and antidiabetic potential. Ethanolic extract was found to be most potent in pharmacological potential as 200mg/kg extract dose exhibited %age pain inhibition of 55.12% and reduced body temperature from 39.78±0.03°C to 37.22±0.02°C in hyperthermic rats. A decrease in blood glucose levels up to 57.88% was observed on the 21st day of the treatment with 500mg/kg ethanolic extract.

The potential of phosphorylated α-synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy.

INTRODUCTION: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by the presence of glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-Syn). Accurate diagnosis and monitoring of MSA present significant challenges, which can lead to potential misdiagnosis and inappropriate treatment. Biomarkers play a crucial role in improving the accuracy of MSA diagnosis, and phosphorylated α-synuclein (p-syn) has emerged as a promising biomarker for aiding in diagnosis and disease monitoring. METHODS: A literature search was conducted on PubMed, Scopus, and Google Scholar using specific keywords and MeSH terms without imposing a time limit. Inclusion criteria comprised various study designs including experimental studies, case-control studies, and cohort studies published only in English, while conference abstracts and unpublished sources were excluded. RESULTS: Increased levels of p-syn have been observed in various samples from MSA patients, such as red blood cells, cerebrospinal fluid, oral mucosal cells, skin, and colon biopsies, highlighting their diagnostic potential. The α-Syn RT-QuIC assay has shown sensitivity in diagnosing MSA and tracking its progression. Meta-analyses and multicenter investigations have confirmed the diagnostic value of p-syn in cerebrospinal fluid, demonstrating high specificity and sensitivity in distinguishing MSA from other neurodegenerative diseases. Moreover, combining p-syn with other biomarkers has further improved the diagnostic accuracy of MSA. CONCLUSION: The p-syn stands out as a promising biomarker for MSA. It is found in oligodendrocytes and shows a correlation with disease severity and progression. However, further research and validation studies are necessary to establish p-syn as a reliable biomarker for MSA. If proven, p-syn could significantly contribute to early diagnosis, disease monitoring, and assessing treatment response.

Analysis of the effectiveness of the latest 4th-generation cryoballoon catheters in pulmonary vein isolation using high-resolution mapping.

BACKGROUND: Long-term data showed that up to 27% of pulmonary veins are reconnected using cryoballoon ablation. This study aimed to evaluate the efficacy of the latest 4th-generation cryoballoon catheters using ultra high-resolution mapping. METHODS: In patients with atrial fibrillation, a standard pulmonary vein isolation (PVI) with the latest 4th-generation cryoballoon catheter (Arctic Front Advance PRO, Medtronic Minneapolis, USA) and the spiral mapping catheter (Achieve Advance, Medtronic, Minneapolis, MN, USA) was performed. Subsequently, high-resolution mapping was achieved using the novel multipolar grid mapping catheter (Advisor HD Grid SE, Abbott Laboratories, USA). Follow-up was obtained after 6 months by means of a 7-day Holter electrocardiogram. RESULTS: In our study, acute PVI was successfully achieved in all 31 patients. The latest 4th-generation cryoballoon catheter is safe in the acute phase of PVI. Additional high-resolution mapping (mean points per map 21,001 ± 4911) using the multipolar grid mapping catheter enabled us to identify residual gaps only in the carina pulmonary vein region; therefore, no additional ablation was performed. Three of 31 patients (10%) presented with atrial arrhythmia recurrence always related with pulmonary vein reconnection; using high-resolution mapping had no additional benefit in identifying pulmonary veins in which reconnection will occur. CONCLUSION: The utility of additional high-density mapping, facilitated by the HD Grid catheter after PVI with the 4th-generation cryoballoon catheter do not substantiate a discernible advantage over conventional mapping methodologies, particularly, the spiral mapping catheter. Residual carinal conduction was observed in a substantial cohort of patients (48%), highlighting a persistent challenge in achieving complete electrical isolation.

Sustained release delivery of favipiravir through statistically optimized, chemically cross-linked, pH-sensitive, swellable hydrogel.

In the current work, favipiravir (an antiviral drug) loaded pH-responsive polymeric hydrogels were developed by the free redical polymerization technique. Box-Behnken design method via Design Expert version 11 was employed to furnish the composition of all hydrogel formulations. Here, polyethylene glycol (PEG) has been utilized as a polymer, acrylic acid (AA) as a monomer, and potassium persulfate (KPS) and methylene-bisacrylamide (MBA) as initiator and cross-linker, respectively. All networks were evaluated for in-vitro drug release (%), sol-gel fraction (%), swelling studies (%), porosity (%), percentage entrapment efficiency, and chemical compatibilities. According to findings, the swelling was pH sensitive and was shown to be greatest at a pH of 6.8 (2500%). The optimum gel fraction offered was 97.8%. A sufficient porosity allows the hydrogel to load a substantial amount of favipiravir despite its hydrophobic behavior. Hydrogels exhibited maximum entrapment efficiency of favipiravir upto 98%. The in-vitro release studies of drug-formulated hydrogel revealed that the drug release from hydrogel was between 85 to 110% within 24 h. Drug-release kinetic results showed that the Korsmeyer Peppas model was followed by most of the developed formulations based on the R2 value. In conclusion, the hydrogel-based technology proved to be an excellent option for creating the sustained-release dosage form of the antiviral drug favipiravir.

Hepatoprotective activity of Lactéol® forte and quercetin dihydrate against thioacetamide-induced hepatic cirrhosis in male albino rats.

Liver cirrhosis is a silent disease in humans and is experimentally induced by many drugs and toxins as thioacetamide (TAA) in particular, which is the typical model for experimental induction of hepatic fibrosis. Thus, the objective of the present study was to elucidate the possible protective effects of lactéol® forte (LF) and quercetin dihydrate (QD) against TAA-induced hepatic damage in male albino rats. Induction of hepatotoxicity was performed by TAA injection (200 mg/kg I/P, twice/ week) in rats. LF (1 × 109 CFU/rat 5 times/week) and QD (50 mg/kg 5 times/week) treated groups were administered concurrently with TAA injection (200 mg/kg I/P, twice/ week). The experimental treatments were conducted for 12 weeks. Hepatotoxicity was evaluated biochemically by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) in the serum and histopathologically with the scoring of histopathological changes besides histochemical assessment of collagen by Masson's trichrome and immunohistochemical analysis for α-smooth muscle actin (α-SMA), Ki67 and caspase-3 expression in liver sections. Our results indicated that LF and QD attenuated some biochemical changes and histochemical markers in TAA-mediated hepatotoxicity in rats by amelioration of biochemical markers and collagen, α-SMA, Ki67 and caspase3 Immunoexpression. Additionally, LF and QD supplementation downregulated the proliferative, necrotic, fibroblastic changes, eosinophilic intranuclear inclusions, hyaline globules and Mallory-like bodies that were detected histopathologically in the TAA group. In conclusion, LF showed better hepatic protection than QD against TAA-induced hepatotoxicity in rats by inhibiting inflammatory reactions with the improvement of some serum hepatic transaminases, histopathological picture and immunohistochemical markers.

Role of GABA pathway in motor and non-motor symptoms in Parkinson's disease: a bidirectional circuit.

Parkinson's disease (PD) is a progressive neurodegenerative disease as a result of the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The fundamental features of PD are motor and non-motor symptoms. PD symptoms develop due to the disruption of dopaminergic neurotransmitters and other neurotransmitters such as γ-aminobutyric acid (GABA). The potential role of GABA in PD neuropathology concerning the motor and non-motor symptoms of PD was not precisely discussed. Therefore, this review intended to illustrate the possible role of GABA in PD neuropathology regarding motor and non-motor symptoms. The GABA pathway is essential in regulating the inhibitory tone to prevent excessive stimulation of the cerebral cortex. Degeneration of dopaminergic neurons in PD is linked with reducing GABAergic neurotransmission. Decreasing GABA activity promotes mitochondrial dysfunction and oxidative stress, which are highly related to PD neuropathology. Hence, restoring GABA activity by GABA agonists may attenuate the progression of PD motor symptoms. Therefore, dysregulation of GABAergic neurons in the SNpc contributes to developing PD motor symptoms. Besides, PD non-motor symptoms are also related to the dysfunction of the GABAergic pathway, and amelioration of this pathway may reduce PD non-motor symptoms. In conclusion, the deregulation of the GABAergic pathway in PD might be intricate in developing motor and non-motor symptoms. Improving this pathway might be a novel, beneficial approach to control PD symptoms.

Exploring the current landscape of single-cell RNA sequencing applications in gastric cancer research.

Gastric cancer (GC) represents a major global health burden and is responsible for a significant number of cancer-related fatalities. Its complex nature, characterized by heterogeneity and aggressive behaviour, poses considerable challenges for effective diagnosis and treatment. Single-cell RNA sequencing (scRNA-seq) has emerged as an important technique, offering unprecedented precision and depth in gene expression profiling at the cellular level. By facilitating the identification of distinct cell populations, rare cells and dynamic transcriptional changes within GC, scRNA-seq has yielded valuable insights into tumour progression and potential therapeutic targets. Moreover, this technology has significantly improved our comprehension of the tumour microenvironment (TME) and its intricate interplay with immune cells, thereby opening avenues for targeted therapeutic strategies. Nonetheless, certain obstacles, including tumour heterogeneity and technical limitations, persist in the field. Current endeavours are dedicated to refining protocols and computational tools to surmount these challenges. In this narrative review, we explore the significance of scRNA-seq in GC, emphasizing its advantages, challenges and potential applications in unravelling tumour heterogeneity and identifying promising therapeutic targets. Additionally, we discuss recent developments, ongoing efforts to overcome these challenges, and future prospects. Although further enhancements are required, scRNA-seq has already provided valuable insights into GC and holds promise for advancing biomedical research and clinical practice.

New insights on testicular cancer prevalence with novel diagnostic biomarkers and therapeutic approaches.

BACKGROUND: Testicular cancer (TC), comprising merely 1% of male neoplasms, holds the distinction of being the most commonly encountered neoplasm among young males. RECENT FINDINGS: Most cases of testicular neoplasms can be classified into two main groups, namely germ cell tumors representing approximately 95% of the cases, and sex cord-stromal tumors accounting for about 5% of the cases. Moreover, its prevalence is on the rise across the globe. TC is a neoplastic condition characterized by a favorable prognosis. The advent of cisplatin-based chemotherapeutic agents in the latter part of the 1970s has led to a significant enhancement in the 5-year survival rate, which presently surpasses 95%. Given that TC is commonly detected before reaching the age of 40, it can be anticipated that these individuals will enjoy an additional 40-50 years of life following successful treatment. The potential causes of TC are multifactorial and related to different pathologies. Accurate identification is imperative to guarantee the utmost efficacious and suitable therapy. To a certain degree, this can be accomplished through the utilization of blood examinations for neoplastic indicators; nonetheless, an unequivocal diagnosis necessitates an evaluation of the histological composition of a specimen via a pathologist. CONCLUSION: TC is multifactorial and has various pathologies, therefore this review aimed to revise the prenatal and postnatal causes as well as novel diagnostic biomarkers and the therapeutic strategies of TC.

Advancements and progress in juvenile idiopathic arthritis: A Review of pathophysiology and treatment.

Juvenile idiopathic arthritis (JIA) is a chronic clinical condition characterized by arthritic features in children under the age of 16, with at least 6 weeks of active symptoms. The etiology of JIA remains unknown, and it is associated with prolonged synovial inflammation and structural joint damage influenced by environmental and genetic factors. This review aims to enhance the understanding of JIA by comprehensively analyzing relevant literature. The focus lies on current diagnostic and therapeutic approaches and investigations into the pathoaetiologies using diverse research modalities, including in vivo animal models and large-scale genome-wide studies. We aim to elucidate the multifactorial nature of JIA with a strong focus towards genetic predilection, while proposing potential strategies to improve therapeutic outcomes and enhance diagnostic risk stratification in light of recent advancements. This review underscores the need for further research due to the idiopathic nature of JIA, its heterogeneous phenotype, and the challenges associated with biomarkers and diagnostic criteria. Ultimately, this contribution seeks to advance the knowledge and promote effective management strategies in JIA.

Awake craniotomies in South America: Advancements, challenges, and future prospects.

BACKGROUND: Awake craniotomy has emerged as an advanced surgical technique, characterized by keeping the patient awake during brain surgery. In South America, awake craniotomies have grained traction in neurosurgical practices across various medical centres and hospitals, with notable practitioners contributing to its growth and refinement in the region. PURPOSE: This study aims to explore the integration and impact of awake craniotomies in South American neurosurgical practices. The focus is on understanding the benefits, challenges, and potential transformative effects of the procedure in the region. RESEARCH DESIGN: A comprehensive narrative review and analysis through a thorough examination of the existing literature. RESULTS: The findings indicate that awake craniotomies in South America offer substantial benefits, including cost savings thorugh reduced hospitalization time, quicker recovery and decreased morbidity. Enhanced safety, effective pain management and reduced anaesthesia also contribute to this. CONCLUSION: Whilst the adaptation of awake craniotomies in South America holds great promise in transforming neurosurgical care in the region, significant challenges hinder its widespread adoption. Inadequate infrastructure, limited access to equipment, financial instability, and shortages in trained healthcare providers represent challenges that need to be addressed.

The role of Aquaporins in tumorigenesis: implications for therapeutic development.

Aquaporins (AQPs) are ubiquitous channel proteins that play a critical role in the homeostasis of the cellular environment by allowing the transit of water, chemicals, and ions. They can be found in many different types of cells and organs, including the lungs, eyes, brain, glands, and blood vessels. By controlling the osmotic water flux in processes like cell growth, energy metabolism, migration, adhesion, and proliferation, AQPs are capable of exerting their regulatory influence over a wide range of cellular processes. Tumour cells of varying sources express AQPs significantly, especially in malignant tumours with a high propensity for metastasis. New insights into the roles of AQPs in cell migration and proliferation reinforce the notion that AQPs are crucial players in tumour biology. AQPs have recently been shown to be a powerful tool in the fight against pathogenic antibodies and metastatic cell migration, despite the fact that the molecular processes of aquaporins in pathology are not entirely established. In this review, we shall discuss the several ways in which AQPs are expressed in the body, the unique roles they play in tumorigenesis, and the novel therapeutic approaches that could be adopted to treat carcinoma.

Therapeutic Potential Effect of Glycogen Synthase Kinase 3 Beta (GSK-3ß) Inhibitors in Parkinson Disease: Exploring an Overlooked Avenue.

Parkinson's disease (PD) is a progressive neurodegenerative disease of the brain due to degeneration of dopaminergic neurons in the substantia nigra (SN). Glycogen synthase kinase 3 beta (GSK-3ß) is implicated in the pathogenesis of PD. Therefore, the purpose of the present review was to revise the mechanistic role of GSK-3ß in PD neuropathology, and how GSK-3ß inhibitors affect PD neuropathology. GSK-3 is a conserved threonine/serine kinase protein that is intricate in the regulation of cellular anabolic and catabolic pathways by modulating glycogen synthase. Over-expression of GSK-3ß is also interconnected with the development of different neurodegenerative diseases. However, the underlying mechanism of GSK-3ß in PD neuropathology is not fully clarified. Over-expression of GSK-3ß induces the development of PD by triggering mitochondrial dysfunction and oxidative stress in the dopaminergic neurons of the SN. NF-κB and NLRP3 inflammasome are activated in response to dysregulated GSK-3ß in PD leading to progressive neuronal injury. Higher expression of GSK-3ß in the early stages of PD neuropathology might contribute to the reduction of neuroprotective brain-derived neurotrophic factor (BDNF). Thus, GSK-3ß inhibitors may be effective in PD by reducing inflammatory and oxidative stress disorders which are associated with degeneration of dopaminergic in the SN.