Pharmacological modulation of Sonic Hedgehog signaling pathways in Angiogenesis: A mechanistic perspective.

The Sonic hedgehog (SHh) signaling pathway is an imperative operating network that helps in regulates the critical events during the development processes like multicellular embryo growth and patterning. Disruptions in SHh pathway regulation can have severe consequences, including congenital disabilities, stem cell renewal, tissue regeneration, and cancer/tumor growth. Activation of the SHh signal occurs when SHh binds to the receptor complex of Patch (Ptc)-mediated Smoothened (Smo) (Ptc-smo), initiating downstream signaling. This review explores how pharmacological modulation of the SHh pathway affects angiogenesis through canonical and non-canonical pathways. The canonical pathway for angiogenesis involves the activation of angiogenic cytokines such as fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), placental growth factor (PGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), stromal cell-derived factor 1α, transforming growth factor-ß1 (TGF-ß1), and angiopoietins (Ang-1 and Ang-2), which facilitate the process of angiogenesis. The Non-canonical pathway includes indirect activation of certain pathways like iNOS/Netrin-1/PKC, RhoA/Rock, ERK/MAPK, PI3K/Akt, Wnt/ß-catenin, Notch signaling pathway, and so on. This review will provide a better grasp of the mechanistic approach of SHh in mediating angiogenesis, which can aid in the suppression of certain cancer and tumor growths.

Wnt signalling pathways as mediators of neuroprotective mechanisms: therapeutic implications in stroke.

A stroke is a complicated neurological illness that occurs when there is a disruption in the blood flow to the brain. This disruption results in the damage of neurons, which then leads to functional abnormalities. The Wnt signalling pathway, which is already well-known for its important function in development and tissue homeostasis, has recently been recognised as a critical factor in the pathophysiology of stroke. Recent studies have shown the Wnt pathway's roles in stroke-related events. The complex-interactions between the Wnt pathway and stroke emphasising the pathway's contributions to neuro-protection and synaptic plasticity. The Wnt pathway's influence on neuro-genesis and synaptic plasticity underscores its potential for driving stroke recovery and rehabilitation strategies. The current review discusses about the Wnt signalling pathway in brain pathophysiology and stroke with special emphasis on the various pathways involved in the positive and negative modulation of Wnt pathway namely Phosphoinositide 3-kinase (PI3-K), Glycogen synthase kinase-3ß (GSK-3ß), Mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.

Targeting inflammatory signaling in obsessive compulsive disorder: a promising approach.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder. Approximately, around 2% to 3% percent of the general population experience symptoms of OCD over the course of their lifetime. OCD can lead to economic burden, poor quality of life, and disability. The characteristic features exhibited generally in OCD are continuous intrusive thoughts and periodic ritualized behaviours. Variations in genes, pathological function of Cortico-Striato-Thalamo-Cortical (CSTC) circuits and dysregulation in the synaptic conduction have been the major factors involved in the pathological progression of OCD. However, the basic mechanisms still largely unknown. Current therapies for OCD largely target monoaminergic neurotransmitters (NTs) in specific dopaminergic and serotonergic circuits. However, such therapies have limited efficacy and tolerability. Drug resistance has been one of the important reasons reported to critically influence the effectiveness of the available drugs. Inflammation has been a crucial factor which is believed to have a significant importance in OCD progression. A significant number of proinflammatory cytokines have been reportedly amplified in patients with OCD. Mechanisms of drug treatment involve attenuation of the symptoms via modulation of inflammatory signalling pathways, modification in brain structure, and synaptic plasticity. Hence, targeting inflammatory signaling may be considered as a suitable approach in the treatment of OCD. The present review focuses mainly on the significant findings from the animal and human studies conducted in this area, that targets inflammatory signaling in neurological conditions. In addition, it also focusses on the therapeutic approaches that target OCD via modification of the inflammatory signaling pathways.

Targeting cardiovascular risk factors with eugenol: an anti-inflammatory perspective.

Inflammation is a multifaceted biological reaction to a wide range of stimuli, and it has been linked to the onset and progression of chronic diseases such as heart disease, cancer, and diabetes. Inflammatory markers found in the blood, including C-reactive protein, serum amyloid A, fibrinogen, plasma viscosity, erythrocyte sedimentation rate, interleukin-6, and soluble adhesion molecules (like intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), are risk factors for cardiovascular diseases such as coronary heart disease, stroke, and peripheral arterial disease. These markers play a crucial role in understanding and assessing cardiovascular health. Due to this complicated relationship between inflammation and cardiovascular disease, anti-inflammatory agents of natural origin have been the subject of many preclinical and clinical studies in recent years. Eugenol is a natural phenolic compound found in clove oil, nutmeg oil, cinnamon oil, and bay leaf oil, as well as other essential oils. Eugenol has been shown to have anti-inflammatory properties in many forms of experimental inflammation. It may scavenge free radicals, which contribute to inflammation and tissue damage. Various studies also suggest that eugenol can limit the production of inflammatory mediators such as prostaglandins, cytokines, and chemokines. Animal models of arthritis, colitis, and lung damage, as well as human clinical studies, have shown that eugenol has phenomenal anti-inflammatory properties. These properties suggest that eugenol may be able to reduce the risk of cardiovascular diseases.

Therapeutic targeting of angiopoietins in tumor angiogenesis and cancer development.

The formation and progression of tumors in humans are linked to the abnormal development of new blood vessels known as neo-angiogenesis. Angiogenesis is a broad word that encompasses endothelial cell migration, proliferation, tube formation, and intussusception, as well as peri-EC recruitment and extracellular matrix formation. Tumor angiogenesis is regulated by angiogenic factors, out of which some of the most potent angiogenic factors such as vascular endothelial growth factor and Angiopoietins (ANGs) in the body are produced by macrophages and other immune cells within the tumor microenvironment. ANGs have a distinct function in tumor angiogenesis and behavior. ANG1, ANG 2, ANG 3, and ANG 4 are the family members of ANG out of which ANG2 has been extensively investigated owing to its unique role in modifying angiogenesis and its tight association with tumor progression, growth, and invasion/metastasis, which makes it an excellent candidate for therapeutic intervention in human malignancies. ANG modulators have demonstrated encouraging outcomes in the treatment of tumor development, either alone or in conjunction with VEGF inhibitors. Future development of more ANG modulators targeting other ANGs is needed. The implication of ANG1, ANG3, and ANG4 as probable therapeutic targets for anti-angiogenesis treatment in tumor development should be also evaluated. The article has described the role of ANG in tumor angiogenesis as well as tumor growth and the treatment strategies modulating ANGs in tumor angiogenesis as demonstrated in clinical studies. The pharmacological modulation of ANGs and ANG-regulated pathways that are responsible for tumor angiogenesis and cancer development should be evaluated for the development of future molecular therapies.

Elevated serum PAR-1 levels as an emerging biomarker of inflammation to predict the dengue infection severity.

The present study was designed to check the serum levels of protease-activated receptor (PAR-1) in patients during different phases of dengue severity. Moreover, a correlation between serum PAR-1 levels and hematological parameters, inflammatory cytokine levels, and liver functional changes was also determined. Based on the World Health Organization criteria, the study population was divided into: nonsevere dengue fever (DF; n = 30), severe dengue hemorrhagic fever (DHF; n = 19), and severe dengue shock syndrome (DSS; n = 11). The platelet count (PLT) and hematocrit (HCT) were analyzed using an automated hematology analyzer and liver function enzymes aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphate (ALP), bilirubin were checked by auto-analyzer using diagnostic kits. Moreover, the levels of inflammatory mediators C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-17 (IL-17), and PAR-1 were determined using respective ELISA kits. The HCT levels were elevated and platelet count decreased significantly during dengue complications (DHF and DSS) compared to the DF patients, while the levels of liver functional biomarkers AST, ALT, ALP, and bilirubin remained elevated in DHF and DSS groups than in the corresponding DF group. Similarly, the inflammatory cytokine levels of CRP, TNF-α, IL-6, and IL-17 in DHF and DSS subjects were markedly increased when observed against DF subjects. Notably, the PAR-1 levels were significantly elevated in DHF and DSS groups than in the DF group and positively correlated with changes in HCT levels, inflammatory biomarkers, and liver enzymes. Our findings conclude that PAR-1 levels persistently increased with the severity of the dengue infection and are strongly associated with various clinical manifestations. Thus, PAR-1 levels can be used as a diagnostic marker for assessing dengue severity.

Imatinib Attenuates Pentylenetetrazole Kindled and Pilocarpine Induced Recurrent Spontaneous Seizures in Mice.

c-Abl is a non-receptor tyrosine kinase that promotes intracellular apoptotic signaling in prolonged epileptic seizures. PTZ and pilocarpine-induced continuous epileptic convulsions cause neuronal death and gliosis. C-Abl is linked to oxidative stress, neuronal hyperexcitability, mitochondrial malfunction, and subsequent seizures. We investigated the involvement of c-Abl in epileptogenesis by employing its selective inhibitor Imatinib (1 & 3 mg/kg; i.p.) together with conventional medication valproate (110 mg/kg; i.p.) tends to be effective in decreasing seizures threshold provoked by PTZ for 15 days and pilocarpine for 37 days. Further, Imatinib was effective in preventing epileptic seizures arbitrated oxidative stress injury. Oxidative stress has been linked to excitotoxicity that is considered to pathogenic factor in epileptic brain damage. As ELIZA and biochemical estimations showed the high level of c-Abl as an indicator of neuronal oxidative and apoptosis under chronic PTZ & pilocarpine epileptic seizures marked by decreased antioxidants and elevated levels of caspase-3 that were successfully prevented with Imatinib treatment same as valproate (standard drug). Further, the aberrant c-Abl activation is also linked with neuroinflammation that is also predisposing factor in the development of seizures. Selective inhibition of c-Abl by Imatinib also showed anti-inflammatory activity marked with suppressed levels of NF-kB and pro-inflammatory mediators (TNF-alpha, IL-1ß, and IL-6) suggesting the neuroprotective effect of Imatinib same as valproate (standard drug) in epilepsy. Therefore, the current study provides preclinical evidence of Imatinib as a potential treatment for seizures, as well as an understanding of potential role of c-Ablin epilepsy.

Brain-Derived Neurotrophic Factor: A Novel Dynamically Regulated Therapeutic Modulator in Neurological Disorders.

The growth factor brain-derived neurotrophic factor (BDNF), and its receptor tropomyosin-related kinase receptor type B (TrkB) play an active role in numerous areas of the adult brain, where they regulate the neuronal activity, function, and survival. Upregulation and downregulation of BDNF expression are critical for the physiology of neuronal circuits and functioning in the brain. Loss of BDNF function has been reported in the brains of patients with neurodegenerative or psychiatric disorders. This article reviews the BDNF gene structure, transport, secretion, expression and functions in the brain. This article also implicates BDNF in several brain-related disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, major depressive disorder, schizophrenia, epilepsy and bipolar disorder.

Biomarkers: Role and Scope in Neurological Disorders.

Neurological disorders pose a great threat to social health and are a major cause for mortality and morbidity. Effective drug development complemented with the improved drug therapy has made considerable progress towards easing symptoms associated with neurological illnesses, yet poor diagnosis and imprecise understanding of these disorders has led to imperfect treatment options. The scenario is complicated by the inability to extrapolate results of cell culture studies and transgenic models to clinical applications which has stagnated the process of improving drug therapy. In this context, the development of biomarkers has been viewed as beneficial to easing various pathological complications. A biomarker is measured and evaluated in order to gauge the physiological process or a pathological progression of a disease and such a marker can also indicate the clinical or pharmacological response to a therapeutic intervention. The development and identification of biomarkers for neurological disorders involves several issues including the complexity of the brain, unresolved discrepant data from experimental and clinical studies, poor clinical diagnostics, lack of functional endpoints, and high cost and complexity of techniques yet research in the area of biomarkers is highly desired. The present work describes existing biomarkers for various neurological disorders, provides support for the idea that biomarker development may ease our understanding underlying pathophysiology of these disorders and help to design and explore therapeutic targets for effective intervention.

Emerging Targets for Modulation of Immune Response and Inflammation in Stroke.

The inflammatory and immunological responses play a significant role after stroke. The innate immune activation stimulated by microglia during stroke results in the migration of macrophages and lymphocytes into the brain and are responsible for tissue damage. The immune response and inflammation following stroke have no defined targets, and the intricacies of the immunological and inflammatory processes are only partially understood. Innate immune cells enter the brain and meninges during the acute phase, which can cause ischemia damage. Activation of systemic immunity is caused by danger signals sent into the bloodstream by injured brain cells, which is followed by a significant immunodepression that encourages life-threatening infections. Neuropsychiatric sequelae, a major source of post-stroke morbidity, may be induced by an adaptive immune response that is initiated by antigen presentation during the chronic period and is directed against the brain. Thus, the current review discusses the role of immune response and inflammation in stroke pathogenesis, their role in the progression of injury during the stroke, and the emerging targets for the modulation of the mechanism of immune response and inflammation that may have possible therapeutic benefits against stroke.

Pharmacological modulation of HIF-1 in the treatment of neuropsychiatric disorders.

Hypoxia-inducible factor 1 has been identified as an important therapeutic target in psychiatric illnesses. Hypoxia is a condition in which tissues do not receive enough oxygen, resulting in less oxidative energy production. HIF-1, the master regulator of molecular response to hypoxia, is destabilized when oxygen levels fall. HIF-1, when activated, increases the gene transcription factors that promote adaptive response and longevity in hypoxia. HIF-regulated genes encode proteins involved in cell survival, energy metabolism, angiogenesis, erythropoiesis, and vasomotor control. Multiple genetic and environmental variables contribute to the pathophysiology of psychiatric disease. This review focuses on the most recent findings indicating the role of oxygen deprivation in CNS damage, with strong attention on HIF-mediated pathways. Several pieces of evidence suggested that, in the case of hypoxia, induction and maintenance of HIF-1 target genes may help reduce nerve damage. Major new insights into the molecular mechanisms that control HIF's sensitivity to oxygen are used to make drugs that can change the way HIF works as a therapeutic target for some CNS diseases.

Vitamin D as therapeutic modulator in cerebrovascular diseases: a mechanistic perspectives.

Vitamin D deficiency has been linked to several major chronic diseases, such as cardiovascular and neurodegenerative diseases, diabetes, and cancer, linked to oxidative stress, inflammation, and aging. Vitamin D deficiency appears to be particularly harmful to the cardiovascular system, as it can cause endothelial dysfunctioning and vascular abnormalities through the modulation of various downstream mechanisms. As a result, new research indicates that therapeutic approaches targeting vitamin D inadequacies or its significant downstream effects, such as impaired autophagy, abnormal pro-inflammatory and pro-oxidant reactions, may delay the onset and severity of major cerebrovascular disorders such as stroke and neurologic malformations. Vitamin D modulates the various molecular pathways, i.e., Nitric Oxide, PI3K-Akt Pathway, cAMP pathway, NF-kB Pathway, Sirtuin 1, Nrf2, FOXO, in cerebrovascular disorder. The current review shows evidence for vitamin D's mitigating or slowing the progression of these cerebrovascular disorders, which are significant causes of disability and death worldwide.

Drug induced nephrotoxicity- A mechanistic approach.

The main goal of the treatment of patients is its effectiveness and safety. However, all currently prescribed drugs being used also have certain adverse effects, which might be seen as an unavoidable but necessary cost of pharmacotherapy. The kidney is the primary organ for xenobiotics elimination, making it particularly susceptible to the harmful effects of drugs and their metabolites during their excretion from the body. Moreover, certain medications have a preferential nephrotoxicity potential, which means that using them increases the risk of kidney injury. Drug nephrotoxicity is, therefore, both a significant problem and a complication of pharmacotherapy. It should be noted that, there is presently no accepted definition of drug-induced nephrotoxicity and no established diagnostic criteria. The current review briefly describes the pathogenic mechanism of drug-induced nephrotoxicity, the various basic drugs with nephrotoxicity potential and the renal biomarkers for the treatment of the drug-related kidney damage.

Exploring various novel diagnostic and therapeutic approaches in treating diabetic retinopathy.

Diabetic retinopathy is regarded as a common manifestation of diabetes mellitus, being a prominent cause of visual impairment and blindness. This microvascular complication is marked by the appearance of microaneurysms, elevated vascular permeability, capillary blockage, and proliferation of neovasculature. The etiology behind retinopathy is ambiguous and the efficacy of current treatment strategies is minimal. Early diagnosis of this complication using a biomarker with high sensitivity and specificity is very essential for providing better therapeutic strategies. The current available therapeutic options are limited with various adverse effects. Laser treatment is not beneficial in all the situations, economic constraints being the major challenge. Surgical interventions are employed when pharmacotherapy and laser treatment fail. New pharmacological treatments are becoming a necessity for treating the condition. This review highlights the use of various diagnostic tools, emerging biomarkers for early detection of diabetic retinopathy, pathological mechanisms associated with the disease, current therapeutic approaches used and future strategies for more enhanced treatment options and more potent pharmacological actions.

Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer's Disease.

No drug on the market, as a single entity, participates in different pathways involved in the pathology of Alzheimer's disease. The current study is aimed at the exploration of multifunctional chalcone derivatives which can act on multiple targets involved in Alzheimer's disease. A series of novel aminoethyl-substituted chalcones have been developed using in silico approaches (scaffold morphing, molecular docking, and ADME) and reported synthetic methods. The synthesized analogs were characterized and evaluated biologically using different in vitro assays against AChE, AGEs, and radical formation. Among all compounds, compound PS-10 was found to have potent AChE inhibitory activity (IC50 = 15.3 nM), even more than the standard drug (IC50 = 15.68 nM). Further, the in vivo evaluation of PS-10 against STZ-induced dementia in rats showed memory improvement (Morris Water Maze test) in rats. Also, PS-10 inhibited STZ-induced brain AChE activity and oxidative stress, further strengthening the observed in vitro effects. Further, the molecular dynamic simulation studies displayed the stability of the PS-10 and AChE complex. The novel aminoethyl-substituted chalcones might be considered potential multifunctional anti-Alzheimer's molecules.

Scaffold Morphing and In Silico Design of Potential BACE-1 (ß-Secretase) Inhibitors: A Hope for a Newer Dawn in Anti-Alzheimer Therapeutics.

Alzheimer's disease (AD) is the prime cause of 65-80% of dementia cases and is caused by plaque and tangle deposition in the brain neurons leading to brain cell degeneration. ß-secretase (BACE-1) is a key enzyme responsible for depositing extracellular plaques made of ß-amyloid protein. Therefore, efforts are being applied to develop novel BACE-1 enzyme inhibitors to halt plaque build-up. In our study, we analyzed some Elenbecestat analogues (a BACE-1 inhibitor currently in clinical trials) using a structure-based drug design and scaffold morphing approach to achieve a superior therapeutic profile, followed by in silico studies, including molecular docking and pharmacokinetics methodologies. Among all the designed compounds, SB306 and SB12 showed good interactions with the catalytic dyad motifs (Asp228 and Asp32) of the BACE-1 enzyme with drug-likeliness properties and a high degree of thermodynamic stability confirmed by the molecular dynamic and stability of the simulated system indicating the inhibitory nature of the SB306 and SB12 on BACE 1.

Therapeutic implications of glucose transporters (GLUT) in cerebral ischemia.

Cerebral ischemia is a leading cause of death in the globe, with a large societal cost. Deprivation of blood flow, together with consequent glucose and oxygen shortage, activates a variety of pathways that result in permanent brain damage. As a result, ischemia raises energy demand, which is linked to significant alterations in brain energy metabolism. Even at the low glucose levels reported in plasma during ischemia, glucose transport activity may adjust to assure the supply of glucose to maintain normal cellular function. Glucose transporters in the brain are divided into two groups: sodium-independent glucose transporters (GLUTs) and sodium-dependent glucose cotransporters (SGLTs).This review assess the GLUT structure, expression, regulation, pathobiology of GLUT in cerebral ischemia and regulators of GLUT and it also provides the synopsis of the literature exploring the relationship between GLUT and the various downstream signalling pathways for e.g., AMP-activated protein kinase (AMPK), CREB (cAMP response element-binding protein), Hypoxia-inducible factor 1 (HIF)-1, Phosphatidylinositol 3-kinase (PI3-K), Mitogen-activated protein kinase (MAPK) and adenylate-uridylate-rich elements (AREs). Therefore, the aim of the present review was to elaborate the therapeutic implications of GLUT in the cerebral ischemia.

α-Lipoic Acid, an Organosulfur Biomolecule a Novel Therapeutic Agent for Neurodegenerative Disorders: An Mechanistic Perspective.

Lipoic acid (α-LA) (1,2-dithiolane3-pentanoic acid (C8H14O2S2) is also called thioctic acid with an oxidized (disulfide, LA) and a reduced (di-thiol: dihydro-lipoic acid, DHLA) form of LA. α-LA is a potent anti-oxidative agent that has a significant potential to treat neurodegenerative disorders. α-LA is both hydrophilic and hydrophobic in nature. It is widely distributed in plants and animals in cellular membranes and in the cytosol, which is responsible for LA's action in both the cytosol and plasma membrane. A systematic literature review of Bentham, Scopus, PubMed, Medline, and EMBASE (Elsevier) databases was carried out to understand the Nature and mechanistic interventions of the α-Lipoic acid for central nervous system diseases. Moreover, α-LA readily crosses the blood-brain barrier, which is a significant factor for CNS activities. The mechanisms of α-LA reduction are highly tissue-specific. α-LA produces its neuroprotective effect by inhibiting reactive oxygen species formation and neuronal damage, modulating protein levels, and promoting neurotransmitters and anti-oxidant levels. Hence, the execution of α-LA as a therapeutic ingredient in the therapy of neurodegenerative disorders is promising. Finally, based on evidence, it can be concluded that α-LA can prevent diseases related to the nervous system.

Poly (ADP-ribose) polymerase: An Overview of Mechanistic Approaches and Therapeutic Opportunities in the Management of Stroke.

Stroke is one of the leading causes of morbidity and mortality accompanied by blood supply loss to a particular brain area. Several mechanistic approaches such as inhibition of poly (ADP-ribose) polymerase, therapies against tissue thrombosis, and neutrophils lead to stroke's therapeutic intervention. Evidence obtained with the poly (ADP-ribose) polymerase (PARP) inhibition and animals having a deficiency of PARP enzymes; represented the role of PARP in cerebral stroke, ischemia/reperfusion, and neurotrauma. PARP is a nuclear enzyme superfamily with various isoforms, each with different structural domains and functions, and out of all, PARP-1 is the best-characterized member. It has been shown to perform multiple physiological as well as pathological processes, including its role in inflammation, oxidative stress, apoptosis, and mitochondrial dysfunction. The enzyme interacts with NF-κB, p53, and other transcriptional factors to regulate survival and cell death and modulates multiple downstream signaling pathways. Clinical trials have also been conducted using PARP inhibitors for numerous disorders and have shown positive results. However, additional information is yet to be established for the therapeutic intervention of PARP inhibitors in stroke. These agents' utilization appears to be challenging due to their unknown potential long-term side effects. PARP activity increased during ischemia, but its inhibition provided significant neuroprotection. Despite the increased interest in PARP as a pharmacological modulator for novel therapeutic therapies, the current review focused on stroke and poly ADP-ribosylation.

Kynurenine Metabolism and Alzheimer's Disease: The Potential Targets and Approaches.

L-tryptophan, an essential amino acid, regulates protein homeostasis and plays a role in neurotransmitter-mediated physiological events. It also influences age-associated neurological alterations and neurodegenerative changes. The metabolism of tryptophan is carried majorly through the kynurenine route, leading to the production of several pharmacologically active enzymes, substrates, and metabolites. These metabolites and enzymes influence a variety of physiological and pathological outcomes of the majority of systems, including endocrine, haemopoietic, gastrointestinal, immunomodulatory, inflammatory, bioenergetic metabolism, and neuronal functions. An extensive literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out to understand the nature of the extensive work done on the kynurenine metabolites that influence cellular redox potential, immunoregulatory mechanisms, inflammatory pathways, cell survival channels, and cellular communication in close association with several neurodegenerative changes. The imbalanced state of kynurenine pathways has found a close association to several pathological disorders, including HIV infections, cancer, autoimmune disorders, neurodegenerative and neurological disorders including Parkinson's disease, epilepsy and has found special attention in Alzheimer's disease (AD). Kynurenine pathway (KP) is intricately linked to AD pathogenesis owing to the influence of kynurenine metabolites on excitotoxic neurotransmission, oxidative stress, uptake of neurotransmitters, and modulation of neuroinflammation, amyloid aggregation, microtubule disruption, and their ability to induce a state of dysbiosis. Pharmacological modulation of KP pathways has shown encouraging results, indicating that it may be a viable and explorable target for the therapy of AD.