Predictive biomarkers of intra-ocular pressure decrease after cataract surgery associated with trabecular washout in patients with pseudo exfoliative glaucoma.

To investigate biomarkers of intra-ocular pressure (IOP) decrease after cataract surgery with trabecular washout in pseudo-exfoliative (PEX) glaucoma. A single-center observational prospective study in PEX glaucoma patients undergoing cataract surgery with trabecular washout (Goniowash) was performed from 2018 to 2021. Age, gender, visual acuity, IOP, endothelial cell count, central corneal thickness, medications, were collected over 16-month follow-up. Multivariable binomial regression models were implemented. 54 eyes (35 subjects) were included. Mean preoperative IOP (IOPBL) was 15.9 ± 3.5 mmHg. Postoperative IOP reduction was significant at 1-month and throughout follow-up (p < 0.01, respectively). IOPBL was a predictive biomarker inversely correlated to IOP decrease throughout follow-up (p < 0.001). At 1 and 12 months of follow-up, IOP decrease concerned 31 (57.4%) and 34 (63.0%) eyes with an average IOP decrease of 17.5% (from 17.6 ± 3.1 to 14.3 ± 2.2 mmHg) and 23.0% (from 17.7 ± 2.8 to 13.5 ± 2.6 mmHg), respectively. Performance (AUC) of IOPBL was 0.85 and 0.94 (p < 0.0001, respectively), with IOPBL threshold ≥ 15 mmHg for 82.1% and 96.8% sensitivity, 84.2% and 75.0% specificity, 1.84 and 3.91 IOP decrease odds-ratio, respectively. All PEX glaucoma patients with IOPBL greater than or equal to the average general population IOP were likely to achieve a significant sustainable postoperative IOP decrease.

Machine learning decision tree models for multiclass classification of common malignant brain tumors using perfusion and spectroscopy MRI data.

Background: To investigate the contribution of machine learning decision tree models applied to perfusion and spectroscopy MRI for multiclass classification of lymphomas, glioblastomas, and metastases, and then to bring out the underlying key pathophysiological processes involved in the hierarchization of the decision-making algorithms of the models. Methods: From 2013 to 2020, 180 consecutive patients with histopathologically proved lymphomas (n = 77), glioblastomas (n = 45), and metastases (n = 58) were included in machine learning analysis after undergoing MRI. The perfusion parameters (rCBVmax, PSRmax) and spectroscopic concentration ratios (lac/Cr, Cho/NAA, Cho/Cr, and lip/Cr) were applied to construct Classification and Regression Tree (CART) models for multiclass classification of these brain tumors. A 5-fold random cross validation was performed on the dataset. Results: The decision tree model thus constructed successfully classified all 3 tumor types with a performance (AUC) of 0.98 for PCNSLs, 0.98 for GBM and 1.00 for METs. The model accuracy was 0.96 with a RSquare of 0.887. Five rules of classifier combinations were extracted with a predicted probability from 0.907 to 0.989 for that end nodes of the decision tree for tumor multiclass classification. In hierarchical order of importance, the root node (Cho/NAA) in the decision tree algorithm was primarily based on the proliferative, infiltrative, and neuronal destructive characteristics of the tumor, the internal node (PSRmax), on tumor tissue capillary permeability characteristics, and the end node (Lac/Cr or Cho/Cr), on tumor energy glycolytic (Warburg effect), or on membrane lipid tumor metabolism. Conclusion: Our study shows potential implementation of machine learning decision tree model algorithms based on a hierarchical, convenient, and personalized use of perfusion and spectroscopy MRI data for multiclass classification of these brain tumors.

WNT/ß-catenin Pathway: a Possible Link Between Hypertension and Alzheimer's Disease.

PURPOSE OF REVIEW: Recent research has shown that older people with high blood pressure (BP), or hypertension, are more likely to have biomarkers of Alzheimer's disease (AD). Essential hypertension represents the most common cardiovascular disease worldwide and is thought to be responsible for about 13% of all deaths. People with essential hypertension who regularly take prescribed BP medications are half as likely to develop AD as those who do not take them. What then is the connection? RECENT FINDINGS: We know that high BP can damage small blood vessels in the brain, affecting those parts that are responsible for memory and thinking. However, the link between AD and hypertension remains unclear. Recent advances in the field of molecular and cellular biology have revealed a downregulation of the canonical WNT/ß-catenin pathway in both hypertension and AD. In AD, the glutamate transport function is decreased, a decrease that is associated with a loss of synapse and neuronal death. ß-catenin signaling appears to act as a major regulator of glutamate transporters (EAAT and GS) expression and can be harnessed to remove excess glutamate in AD. This review focuses on the possible link between hypertension and AD through the decreased WNT/ß-catenin which interacts with the glutamatergic pathway.

WNT/ß-catenin pathway and circadian rhythms in obsessive-compulsive disorder.

The neuropsychiatric disease named obsessive-compulsive disorder is composed by obsessions and/or compulsions. Obsessive-compulsive disorder etiologies are undefined. However, numerous mechanisms in several localizations are implicated. Some studies showed that both glutamate, inflammatory factors and oxidative stress could have main functions in obsessive-compulsive disorder. Glycogen synthase kinase-3ß, the major negative controller of the WNT/ß-catenin pathway is upregulated in obsessive-compulsive disorder. In obsessive-compulsive disorder, some studies presented the actions of the different circadian clock genes. WNT/ß-catenin pathway and circadian clock genes appear to be intricate. Thus, this review focuses on the interaction between circadian clock genes and the WNT/ß-catenin pathway in obsessive-compulsive disorder.

Theoretical discrimination index of postural instability in amyotrophic lateral sclerosis.

To assess the usefulness of a theoretical postural instability discrimination index (PIth) in amyotrophic lateral sclerosis (ALS). Prospective regression analyzes were performed to identify the biomechanical determinants of postural instability unrelated to lower limb motor deficits from gait initiation factors. PIth was constructed using a logit function of biomechanical determinants. Discriminatory performance and performance differences were tested. Backward displacement of the pression center (APAamplitude) and active vertical braking of the mass center (Braking-index) were the biomechanical determinants of postural instability. PIth = - 0.13 × APAamplitude - 0.12 × Braking-index + 5.67, (P < 0.0001, RSquare = 0.6119). OR (APAamplitude) and OR (Braking-index) were 0.878 and 0.887, respectively, i.e., for a decrease of 10 mm in APAamplitude or 10% in Braking-index, the postural instability risk was 11.391 or 11.274 times higher, respectively. PIth had the highest discriminatory performance (AUC 0.953) with a decision threshold value [Formula: see text] 0.587, a sensitivity of 90.91%, and a specificity of 83.87%, significantly increasing the sensitivity by 11.11%. PIth, as objective clinical integrator of gait initiation biomechanical processes significantly involved in dynamic postural control, was a reliable and performing discrimination index of postural instability with a significant increased sensitivity, and may be useful for a personalized approach to postural instability in ALS.

Possible actions of cannabidiol in obsessive-compulsive disorder by targeting the WNT/ß-catenin pathway.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder characterized by recurrent and distinctive obsessions and/or compulsions. The etiologies remain unclear. Recent findings have shown that oxidative stress, inflammation, and glutamatergic pathways play key roles in the causes of OCD. However, first-line therapies include cognitive-behavioral therapy but only 40% of the patients respond to this first-line therapy. Research for new treatment is mandatory. This review focuses on the potential effects of cannabidiol (CBD), as a potential therapeutic strategy, on OCD and some of the presumed mechanisms by which CBD provides its benefit properties. CBD medication downregulates GSK-3ß, the main inhibitor of the WNT/ß-catenin pathway. The activation of the WNT/ß-catenin could be associated with the control of oxidative stress, inflammation, and glutamatergic pathway and circadian rhythms dysregulation in OCD. Future prospective clinical trials could focus on CBD and its different and multiple interactions in OCD.

The Key Role of the WNT/ß-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions.

The canonical WNT/ß-catenin pathway is upregulated in cancers and plays a major role in proliferation, invasion, apoptosis and angiogenesis. Nuclear ß-catenin accumulation is associated with cancer. Hypoxic mechanisms lead to the activation of the hypoxia-inducible factor (HIF)-1α, promoting glycolytic and energetic metabolism and angiogenesis. However, HIF-1α is degraded by the HIF prolyl hydroxylase under normoxia, conditions under which the WNT/ß-catenin pathway can activate HIF-1α. This review is therefore focused on the interaction between the upregulated WNT/ß-catenin pathway and the metabolic processes underlying cancer mechanisms under normoxic conditions. The WNT pathway stimulates the PI3K/Akt pathway, the STAT3 pathway and the transduction of WNT/ß-catenin target genes (such as c-Myc) to activate HIF-1α activity in a hypoxia-independent manner. In cancers, stimulation of the WNT/ß-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. The activation of the Wnt/ß-catenin pathway induces gene transactivation via WNT target genes, c-Myc and cyclin D1, or via HIF-1α. This in turn encodes aerobic glycolysis enzymes, including glucose transporter, hexokinase 2, pyruvate kinase M2, pyruvate dehydrogenase kinase 1 and lactate dehydrogenase-A, leading to lactate production. The increase in lactate production is associated with modifications to the tumor microenvironment and tumor growth under normoxic conditions. Moreover, increased lactate production is associated with overexpression of VEGF, a key inducer of angiogenesis. Thus, under normoxic conditions, overstimulation of the WNT/ß-catenin pathway leads to modifications of the tumor microenvironment and activation of the Warburg effect, autophagy and glutaminolysis, which in turn participate in tumor growth.

PPARγ Agonists: Emergent Therapy in Endometriosis.

Endometriosis is one of the major gynecological diseases of reproductive-age women. This disease is characterized by the presence of glands and stroma outside the uterine cavity. Several studies have shown the major role of inflammation, angiogenesis, adhesion and invasion, and apoptosis in endometriotic lesions. Nevertheless, the mechanisms underlying endometriotic mechanisms still remain unclear and therapies are not currently efficient. The introduction of new agents can be effective by improving the condition of patients. PPARγ ligands can directly modulate these pathways in endometriosis. However, data in humans remain low. Thus, the purpose of this review is to summarize the potential actions of PPARγ agonists in endometriosis by acting on inflammation, angiogenesis, invasion, adhesion, and apoptosis.

Opposed Interplay between IDH1 Mutations and the WNT/ß-Catenin Pathway: Added Information for Glioma Classification.

Gliomas are the main common primary intraparenchymal brain tumor in the central nervous system (CNS), with approximately 7% of the death caused by cancers. In the WHO 2016 classification, molecular dysregulations are part of the definition of particular brain tumor entities for the first time. Nevertheless, the underlying molecular mechanisms remain unclear. Several studies have shown that 75% to 80% of secondary glioblastoma (GBM) showed IDH1 mutations, whereas only 5% of primary GBM have IDH1 mutations. IDH1 mutations lead to better overall survival in gliomas patients. IDH1 mutations are associated with lower stimulation of the HIF-1α a, aerobic glycolysis and angiogenesis. The stimulation of HIF-1α and the process of angiogenesis appears to be activated only when hypoxia occurs in IDH1-mutated gliomas. In contrast, the observed upregulation of the canonical WNT/ß-catenin pathway in gliomas is associated with proliferation, invasion, aggressive-ness and angiogenesis.. Molecular pathways of the malignancy process are involved in early stages of WNT/ß-catenin pathway-activated-gliomas, and this even under normoxic conditions. IDH1 mutations lead to decreased activity of the WNT/ß-catenin pathway and its enzymatic targets. The opposed interplay between IDH1 mutations and the canonical WNT/ß-catenin pathway in gliomas could participate in better understanding of the observed evolution of different tumors and could reinforce the glioma classification.

Lithium: a potential therapeutic strategy in obsessive-compulsive disorder by targeting the canonical WNT/ß pathway.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder characterized b-y recurrent and distinctive obsessions and/or compulsions. The etiologies remain unclear. Recent findings have shown that oxidative stress, inflammation, and the glutamatergic pathway play key roles in the causes of OCD. However, first-line therapies include cognitive-behavioral therapy but only 40% of the patients respond to this first-line therapy. Research for a new treatment is mandatory. This review focuses on the potential effects of lithium, as a potential therapeutic strategy, on OCD and some of the presumed mechanisms by which lithium provides its benefit properties. Lithium medication downregulates GSK-3ß, the main inhibitor of the WNT/ß-catenin pathway. The activation of the WNT/ß-catenin could be associated with the control of oxidative stress, inflammation, and glutamatergic pathway. Future prospective clinical trials could focus on lithium and its different and multiple interactions in OCD.

Potential role of cannabidiol in Parkinson's disease by targeting the WNT/ß-catenin pathway, oxidative stress and inflammation.

Parkinson's disease (PD) is a major neurodegenerative disease (ND), presenting a progressive degeneration of the nervous system characterized by a loss of dopamine in the substantia nigra pars compacta. Recent findings have shown that oxidative stress and inflammation play key roles in the development of PD. However, therapies remain uncertain and research for new treatment is of the utmost importance. This review focuses on the potential effects of using cannabidiol (CBD) as a potential therapeutic strategy for the treatment of PD and on some of the presumed mechanisms by which CBD provides its beneficial properties. CBD medication downregulates GSK-3ß, the main inhibitor of the WNT/ß-catenin pathway. Activation of the WNT/ß-catenin could be associated with the control of oxidative stress and inflammation. Future prospective clinical trials should focus on CBD and its multiple interactions in the treatment of PD.

Interplay of Opposing Effects of the WNT/ß-Catenin Pathway and PPARγ and Implications for SARS-CoV2 Treatment.

The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has quickly reached pandemic proportions. Cytokine profiles observed in COVID-19 patients have revealed increased levels of IL-1ß, IL-2, IL-6, and TNF-α and increased NF-κB pathway activity. Recent evidence has shown that the upregulation of the WNT/ß-catenin pathway is associated with inflammation, resulting in a cytokine storm in ARDS (acute respire distress syndrome) and especially in COVID-19 patients. Several studies have shown that the WNT/ß-catenin pathway interacts with PPARγ in an opposing interplay in numerous diseases. Furthermore, recent studies have highlighted the interesting role of PPARγ agonists as modulators of inflammatory and immunomodulatory drugs through the targeting of the cytokine storm in COVID-19 patients. SARS-CoV2 infection presents a decrease in the angiotensin-converting enzyme 2 (ACE2) associated with the upregulation of the WNT/ß-catenin pathway. SARS-Cov2 may invade human organs besides the lungs through the expression of ACE2. Evidence has highlighted the fact that PPARγ agonists can increase ACE2 expression, suggesting a possible role for PPARγ agonists in the treatment of COVID-19. This review therefore focuses on the opposing interplay between the canonical WNT/ß-catenin pathway and PPARγ in SARS-CoV2 infection and the potential beneficial role of PPARγ agonists in this context.

Lithium and Atypical Antipsychotics: The Possible WNT/ß Pathway Target in Glaucoma.

Glaucoma is a progressive neurodegenerative disease that represents the major cause of irreversible blindness. Recent findings have shown which oxidative stress, inflammation, and glutamatergic pathway have main roles in the causes of glaucoma. Lithium is the major commonly used drug for the therapy of chronic mental illness. Lithium therapeutic mechanisms remain complex, including several pathways and gene expression, such as neurotransmitter and receptors, circadian modulation, ion transport, and signal transduction processes. Recent studies have shown that the benefits of lithium extend beyond just the therapy of mood. Neuroprotection against excitotoxicity or brain damages are other actions of lithium. Moreover, recent findings have investigated the role of lithium in glaucoma. The combination of lithium and atypical antipsychotics (AAPs) has been the main common choice for the treatment of bipolar disorder. Due to the possible side effects gradually introduced in therapy. Currently, no studies have focused on the possible actions of AAPs in glaucoma. Recent studies have shown a down regulation of the WNT/ß-catenin pathway in glaucoma, associated with the overactivation of the GSK-3ß signaling. The WNT/ß-catenin pathway is mainly associated with oxidative stress, inflammation and glutamatergic pathway. Lithium is correlated with upregulation the WNT/ß-catenin pathway and downregulation of the GSK-3ß activity. Thus, this review focuses on the possible actions of lithium and AAPs, as possible therapeutic strategies, on glaucoma and some of the presumed mechanisms by which these drugs provide their possible benefit properties through the WNT/ß-catenin pathway.

Cannabidiol and the Canonical WNT/ß-Catenin Pathway in Glaucoma.

Glaucoma is a progressive neurodegenerative disease which constitutes the main frequent cause of irreversible blindness. Recent findings have shown that oxidative stress, inflammation and glutamatergic pathway play key roles in the causes of glaucoma. Recent studies have shown a down regulation of the WNT/ß-catenin pathway in glaucoma, associated with overactivation of the GSK-3ß signaling. WNT/ß-catenin pathway is mainly associated with oxidative stress, inflammation and glutamatergic pathway. Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa plant which possesses many therapeutic properties across a range of neuropsychiatric disorders. Since few years, CBD presents an increased interest as a possible drug in anxiolytic disorders. CBD administration is associated with increase of the WNT/ß-catenin pathway and decrease of the GSK-3ß activity. CBD has a lower affinity for CB1 but can act through other signaling in glaucoma, including the WNT/ß-catenin pathway. CBD downregulates GSK3-ß activity, an inhibitor of WNT/ß-catenin pathway. Moreover, CBD was reported to suppress pro-inflammatory signaling and neuroinflammation, oxidative stress and glutamatergic pathway. Thus, this review focuses on the potential effects of cannabidiol, as a potential therapeutic strategy, on glaucoma and some of the presumed mechanisms by which this phytocannabinoid provides its possible benefit properties through the WNT/ß-catenin pathway.

Parkinson's Disease: Potential Actions of Lithium by Targeting the WNT/ß-Catenin Pathway, Oxidative Stress, Inflammation and Glutamatergic Pathway.

Parkinson's disease (PD) is one of the major neurodegenerative diseases (ND) which presents a progressive neurodegeneration characterized by loss of dopamine in the substantia nigra pars compacta. It is well known that oxidative stress, inflammation and glutamatergic pathway play key roles in the development of PD. However, therapies remain uncertain and research for new treatment is mandatory. This review focuses on the potential effects of lithium, as a potential therapeutic strategy, on PD and some of the presumed mechanisms by which lithium provides its benefit properties. Lithium medication downregulates GSK-3beta, the main inhibitor of the WNT/ß-catenin pathway. The stimulation of the WNT/ß-catenin could be associated with the control of oxidative stress, inflammation, and glutamatergic pathway. Future prospective clinical trials could focus on lithium and its different and multiple interactions in PD.

Altered phospholipid and high-energy phosphate metabolism in the basal ganglia and thalamus of severe obsessive compulsive patients with treatment resistance: A phosphorus 31 nuclear magnetic resonance spectroscopy study.

INTRODUCTION: Cerebral metabolism in obsessive-compulsive-disorder(OCD) has been the subject of numerous studies using proton magnetic resonance spectroscopy(MRS). Despite heterogeneous results, some studies have unraveled membrane turnover and energy metabolism abnormalities in different brain regions, suggesting that alterations in these processes may contribute to the pathophysiology. So far, no authors have explored phospholipids and high-energy phosphate metabolism using 31P-MRS, which allows in vivo quantification of phosphorus metabolites that are considered to be related to membrane turnover and energy metabolism. MATERIALS AND METHODS: The aim of our study was to describe and compare brain metabolic changes using 31P-MRS in the striatum and the thalamus, between 23 severe OCD patients and 22 healthy controls. All subject underwent a clinical examination and a same 31P-MRS protocol. RESULTS: Significantly, increased concentrations of PC, PDE,PME,GPC,PME/PCr,PDE/PCr were found in patients compared to controls in the striatum and the thalamus. PCr and tATP were decreased in the striatum. Finally, significant correlations were found in the striatum and the thalamus between illness duration and some specific measured parameters. CONCLUSION: Our results showed significant modifications of the membrane and energy metabolism in the basal ganglia of severe OCD patients and suggests a link between energetic buffer and serotonin metabolism disorder.

The influence of circadian rhythms and aerobic glycolysis in autism spectrum disorder.

Intellectual abilities and their clinical presentations are extremely heterogeneous in autism spectrum disorder (ASD). The main causes of ASD remain unclear. ASD is frequently associated with sleep disorders. Biologic rhythms are complex systems interacting with the environment and controlling several physiological pathways, including brain development and behavioral processes. Recent findings have shown that the deregulation of the core clock neurodevelopmental signaling is correlated with ASD clinical presentation. One of the main pathways involved in developmental cognitive disorders is the canonical WNT/ß-catenin pathway. Circadian clocks have a main role in some tissues by driving circadian expression of genes involved in physiologic and metabolic functions. In ASD, the increase of the canonical WNT/ß-catenin pathway is enhancing by the dysregulation of circadian rhythms. ASD progression is associated with a major metabolic reprogramming, initiated by aberrant WNT/ß-catenin pathway, the aerobic glycolysis. This review focuses on the interest of circadian rhythms dysregulation in metabolic reprogramming in ASD through the aberrant upregulation of the canonical WNT/ß-catenin pathway.

Riluzole: a therapeutic strategy in Alzheimer's disease by targeting the WNT/ß-catenin pathway.

Alzheimer's disease (AD) is a neurodegenerative disease, where the etiology remains unclear. AD is characterized by amyloid-(Aß) protein aggregation and neurofibrillary plaques deposits. Oxidative stress and chronic inflammation have been suggested as causes of AD. Glutamatergic pathway dysregulation is also mainly associated with AD process. In AD, the canonical WNT/ß-catenin pathway is downregulated. Downregulation of WNT/ß-catenin, by activation of GSK-3ß-induced Aß, and inactivation of PI3K/Akt pathway involve oxidative stress in AD. The downregulation of the WNT/ß-catenin pathway decreases the activity of EAAT2, the glutamate receptors, and leads to neuronal death. In AD, oxidative stress, neuroinflammation and glutamatergic pathway operate in a vicious circle driven by the dysregulation of the WNT/ß-catenin pathway. Riluzole is a glutamate modulator and used as treatment in amyotrophic lateral sclerosis. Recent findings have highlighted its use in AD and its potential increase power on the WNT pathway. Nevertheless, the mechanism by which Riluzole can operate in AD remains unclear and should be better determine. The focus of our review is to highlight the potential action of Riluzole in AD by targeting the canonical WNT/ß-catenin pathway to modulate glutamatergic pathway, oxidative stress and neuroinflammation.

Circadian Rhythms in Exudative Age-Related Macular Degeneration: The Key Role of the Canonical WNT/ß-Catenin Pathway.

Age-related macular degeneration (AMD) is considered as the main worldwide cause of blindness in elderly adults. Exudative AMD type represents 10 to 15% of macular degeneration cases, but is the main cause of vision loss and blindness. Circadian rhythm changes are associated with aging and could further accelerate it. However, the link between circadian rhythms and exudative AMD is not fully understood. Some evidence suggests that dysregulation of circadian functions could be manifestations of diseases or could be risk factors for the development of disease in elderly adults. Biological rhythms are complex systems interacting with the environment and control several physiological pathways. Recent findings have shown that the dysregulation of circadian rhythms is correlated with exudative AMD. One of the main pathways involved in exudative AMD is the canonical WNT/ß-catenin pathway. Circadian clocks have a main role in some tissues by driving the circadian expression of genes involved in physiological and metabolic functions. In exudative AMD, the increase of the canonical WNT/ß-catenin pathway is enhanced by the dysregulation of circadian rhythms. Exudative AMD progression is associated with major metabolic reprogramming, initiated by aberrant WNT/ß-catenin pathway, of aerobic glycolysis. This review focuses on the interest of circadian rhythm dysregulation in exudative AMD through the aberrant upregulation of the canonical WNT/ß-catenin pathway.

Circadian rhythms, Neuroinflammation and Oxidative Stress in the Story of Parkinson's Disease.

Parkinson's disease (PD) is one of the main neurodegenerative disease characterized by a progressive degeneration of neurons constituted by dopamine in the substantia nigra pars compacta. The etiologies of PD remain unclear. Aging is the main risk factor for PD. Aging could dysregulate molecular pathways controlling cell homeostatic mechanisms. PD cells are the sites of several metabolic abnormalities including neuroinflammation and oxidative stress. Metabolic structures are driven by circadian rhythms. Biologic rhythms are complex systems interacting with the environment and controlling several physiological pathways. Recent findings have shown that the dysregulation of the circadian rhythms is correlated with PD and its metabolic dysregulations. This review is focused on the key role of circadian rhythms and their impact on neuroinflammation and oxidative stress in Parkinson's disease.