Sonic hedgehog signalling pathway contributes in age-related disorders and Alzheimer's disease.

Alzheimer's disease (AD) is caused by the aging process and manifested by cognitive deficits and progressive memory loss. During aging, several conditions, including hypertension, diabetes, and cholesterol, have been identified as potential causes of AD by affecting Sonic hedgehog (Shh) signalling. In addition to being essential for cell differentiation and proliferation, Shh signalling is involved in tissue repair and the prevention of neurodegeneration.

2D-QSAR, molecular docking and MD simulation based virtual screening of the herbal molecules against Alzheimer's disorder: an approach to predict CNS activity.

Acetylcholinesterase (AChE) is one of the key enzyme targets that have been used clinically for the management of Alzheimer's Disorder (AD). Numerous reports in the literature predict and demonstrate , and anticholinergic activity of herbal molecules, however, majority of them failed to find clinical application. To address these issues, we developed a 2D-QSAR model that could efficiently predict the AChE inhibitory activity of herbal molecules along with predicting their potential to cross the blood-brain-barrier (BBB) to exert their beneficial effects during AD.

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.

Epigenetics and Gut Microbiota Crosstalk: A potential Factor in Pathogenesis of Cardiovascular Disorders.

Cardiovascular diseases (CVD) are the leading cause of mortality, morbidity, and "sudden death" globally. Environmental and lifestyle factors play important roles in CVD susceptibility, but the link between environmental factors and genetics is not fully established. Epigenetic influence during CVDs is becoming more evident as its direct involvement has been reported.

Molecular Insights to the Wnt Signaling During Alzheimer's Disorder: a Potential Target for Therapeutic Interventions.

In the adult brain, Wnt signaling is crucial for neurogenesis, and it also regulates neuronal development, neuronal maturation, neuronal differential, and proliferation. Impaired Wnt signaling pathways are associated with enhanced levels of amyloid-β, reduced β-catenin levels, and increased expression of GSK-3β enzyme, suggesting its direct association with the pathogenesis of Alzheimer's disorder (AD). These findings are consolidated by reports where activation of Wnt signaling by genetic factors and pharmacological intervention has improved the cognitive functions in animals and restored neurogenesis in the adult brain.

Exploring the Role of Autophagy Dysfunction in Neurodegenerative Disorders.

Autophagy is a catabolic pathway by which misfolded proteins or damaged organelles are engulfed by autophagosomes and then transported to lysosomes for degradation. Recently, a great improvement has been done to explain the molecular mechanisms and roles of autophagy in several important cellular metabolic processes. Besides being a vital clearance pathway or a cell survival pathway in response to different stresses, autophagy dysfunction, either upregulated or down-regulated, has been suggested to be linked with numerous neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic lateral sclerosis.

Elucidating the Possible Role of FoxO in Depression.

Forkhead box-O (FoxO) transcriptional factors perform essential functions in several physiological and biological processes. Recent studies have shown that FoxO is implicated in the pathophysiology of depression. Changes in the upstream mediators of FoxOs including brain-derived neurotrophic factor (BDNF) and protein kinase B have been associated with depressive disorder and the antidepressant agents are known to alter the phosphorylation of FoxOs.

Reckoning γ-Glutamyl-S-allylcysteine as a potential main protease (m) inhibitor of novel SARS-CoV-2 virus identified using docking and molecular dynamics simulation.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 or COVID-19), outbreak was first reported in December 2019 in the Wuhan, China. COVID-19 managed to spread worldwide and so far more than 9.1 million cases and more than 4.

Phytochemicals from Plant Foods as Potential Source of Antiviral Agents: An Overview.

To date, the leading causes of mortality and morbidity worldwide include viral infections, such as Ebola, influenza virus, acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) and recently COVID-19 disease, caused by the SARS-CoV-2 virus. Currently, we can count on a narrow range of antiviral drugs, especially older generation ones like ribavirin and interferon which are effective against viruses in vitro but can often be ineffective in patients. In addition to these, we have antiviral agents for the treatment of herpes virus, influenza virus, HIV and hepatitis virus.

Stressed mitochondria: A target to intrude alzheimer's disease.

Alzheimer's disease (AD) is the inoperable, incapacitating, neuropsychiatric, and degenerative manifestation that drastically affects human life quality. The current medications target extra-neuronal senile plaques, oxidative stress, neuroinflammation, intraneuronal neurofibrillary tangles, cholinergic deficits, and excitotoxicity. Among novel pathways and targets, bioenergetic and resultant mitochondrial dysfunction has been recognized as essential factors that decide the neuronal fate and consequent neurodegeneration in AD.

Gut Microbiota Composition and Epigenetic Molecular Changes Connected to the Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder, and its pathogenesis is not fully known. Although there are several hypotheses, such as neuroinflammation, tau hyperphosphorylation, amyloid-β plaques, neurofibrillary tangles, and oxidative stress, none of them completely explain the origin and progression of AD. Emerging evidence suggests that gut microbiota and epigenetics can directly influence the pathogenesis of AD via their effects on multiple pathways, including neuroinflammation, oxidative stress, and amyloid protein.

Exploring Sonic Hedgehog Cell Signaling in Neurogenesis: Its Potential Role in Depressive Behavior.

Depression is the most prevalent form of neuropsychiatric disorder affecting all age groups globally. As per the estimation of the World Health Organization (WHO), depression will develop into the foremost reason for disability globally by the year 2030. The primary neurobiological mechanism implicated in depression remains ambiguous; however, dysregulation of molecular and signaling transductions results in depressive disorders.

CNS implications of COVID-19: a comprehensive review.

COVID-19 was first reported in December 2019 in the Wuhan city of China, and since then it has spread worldwide taking a heavy toll on human life and economy. COVID-19 infection is commonly associated with symptoms like coughing, fever, and shortness of breath, besides, the reports of muscle pain, anosmia, hyposmia, and loss of taste are becoming evident. Recent reports suggest the pathogenic invasion of the SARS-CoV-2 into the CNS, that could thereby result in devastating long term complications, primarily because some of these complications may go unnoticed for a long time.

Exploring the Various Aspects of Brain-Derived Neurotropic Factor (BDNF) in Diabetes Mellitus.

Brain-Derived Neurotrophic Factor (BDNF) serves as a modulator for neurotransmitters by participating in neuronal plasticity, essential for their growth and neuronal survival. It also shows a wide range of expression patterns in the systemic and peripheral tissues; thereby, its biological actions are not just limited to the CNS but may a vital role in peripheral disorders, such as Diabetes Mellitus (DM). Platelets serve as one of the major sources of BDNF, which regulates energy homeostasis and glucose metabolism by participating in the expression of specific pro-survival genes.

Molecular insights into the therapeutic promise of targeting HMGB1 in depression.

Depression is a common psychiatric disorder, the exact pathogenesis of which is still elusive. Studies have proposed that immunity disproportion and enhancement in proinflammatory cytokines might be linked with the development of depression. HMGB1 (High-mobility group box (1) protein has obtained more interest as an essential factor in inherent immune reactions and a regulating factor in various inflammation-related diseases.

Ubiquitination in rheumatoid arthritis.

Rheumatoid arthritis is a chronic, inflammatory joint disease leading to inflammation of synovial membrane that lines the joints. This inflammation further progresses and results in destruction of joints and surrounding cartilages. The underlying factors can be oxidative stress, pro-inflammatory mediators, imbalance and attenuation between various enzymes and proteins (like nuclear factor erythroid 2 related factor 2/Nrf2 and ubiquitin).

Distinctive Evidence Involved in the Role of Endocannabinoid Signalling in Parkinson's Disease: A Perspective on Associated Therapeutic Interventions.

Current pharmacotherapy of Parkinson's disease (PD) is symptomatic and palliative, with levodopa/carbidopa therapy remaining the prime treatment, and nevertheless, being unable to modulate the progression of the neurodegeneration. No available treatment for PD can enhance the patient's life-quality by regressing this diseased state. Various studies have encouraged the enrichment of treatment possibilities by discovering the association of the effects of the endocannabinoid system (ECS) in PD.

Gene Therapy in the Management of Parkinson's Disease: Potential of GDNF as a Promising Therapeutic Strategy.

The limitations of conventional treatment therapies in Parkinson's disorder, a common neurodegenerative disorder, lead to the development of an alternative gene therapy approach. Multiple treatment options targeting dopaminergic neuronal regeneration, production of enzymes linked with dopamine synthesis, subthalamic nucleus neurons, regulation of astrocytes and microglial cells and potentiating neurotrophic factors, were established. Viral vector-based dopamine delivery, prodrug approaches, fetal ventral mesencephalon tissue transplantation and dopamine synthesizing enzyme encoding gene delivery are significant therapies evidently supported by numerous trials.

Exploring the therapeutic promise of targeting HMGB1 in rheumatoid arthritis.

High mobility group box-1 (HMGB1) protein is a diverse, single polypeptide moiety, present in mammalian eukaryotic cells. In response to stimuli, this nuclear protein is actively secreted in to the extracellular compartment or passively released by the necrotic cells, in order to mediate inflammatory responses, by forming complexes with IL-1α, IL-1β, LPS and other moieties, and binding to RAGE, TLR and other receptor ligands, initiating downstream, signaling processes. This molecule acts as a proinflammatory cytokine and contributes to the progression of diseases like, acute lung injury, autoimmune liver damage, graft rejection immune response and arthritis.

Nutraceuticals in Neurological Disorders.

Neurological diseases are one of the major healthcare issues worldwide. Posed lifestyle changes are associated with drastically increased risk of chronic illness and diseases, posing a substantial healthcare and financial burden to society globally. Researchers aim to provide fine treatment for ailing disorders with minimal exposed side effects.

Dysregulation of the Gut-Brain Axis, Dysbiosis and Influence of Numerous Factors on Gut Microbiota Associated Parkinson's Disease.

Background: Parkinson's disease (PD) has been one of the substantial social, medical concerns and, burdens of the present time. PD is a gradually devastating neurodegenerative disorder of the neurological function marked with α-synucleinopathy affecting numerous regions of the brain-gut axis, as well as the central, enteric, and autonomic nervous system. Its etiology is a widely disputed topic.

Alzheimer's Disorder: Epigenetic Connection and Associated Risk Factors.

The gene based therapeutics and drug targets have shown incredible and appreciable advances in alleviating human sufferings and complexities. Epigenetics simply means above genetics or which controls the organism beyond genetics. At present it is very clear that all characteristics of an individual are not determined by DNA alone, rather the environment, stress, life style and nutrition play a vital part in determining the response of an organism.

Computational and In-Vitro Validation of Natural Molecules as Potential Acetylcholinesterase Inhibitors and Neuroprotective Agents.

Background: Cholinesterase inhibitors are the first line of therapy for the management of Alzheimer's disease (AD), however, it is now established that they provide only temporary and symptomatic relief, besides, having several inherited side-effects. Therefore, an alternative drug discovery method is used to identify new and safer 'disease-modifying drugs'.

Methods: Herein, we screened 646 small molecules of natural origin having reported pharmacological and functional values through in-silico docking studies to predict safer neuromodulatory molecules with potential to modulate acetylcholine metabolism.

Type 2 Diabetes Mellitus Is Associated with Social Recognition Memory Deficit and Altered Dopaminergic Neurotransmission in the Amygdala.

Objective: Diabetic neuropathy is a chronic and often disabling condition that affects a significant number of individuals with diabetes mellitus (DM). It is now established that DM causes various CNS complications like Alzheimer's, dementia, anxiety, depression, neurodegeneration, mood disorders, cognitive dysfunctioning, and so on. Since amygdala and dopaminergic circuitry are critical in controlling several aspects of social behavior, even social recognition memory (SRM), we aimed to study the expression analysis of dopaminergic circuitry in amygdala using real-time polymerase chain reaction.