Drug repurposing: A multi targetted approach to treat cardiac disease from existing classical drugs to modern drug discovery.

Cardiovascular diseases (CVDs) are characterized by abnormalities in the heart, blood vessels, and blood flow. CVDs comprise a diverse set of health issues. There are several types of CVDs like stroke, endothelial dysfunction, thrombosis, atherosclerosis, plaque instability and heart failure. Identification of a new drug for heart disease takes longer duration and its safety efficacy test takes even longer duration of research and approval. This chapter explores drug repurposing, nano-therapy, and plant-based treatments for managing CVDs from existing drugs which saves time and safety issues with testing new drugs. Existing drugs like statins, ACE inhibitor, warfarin, beta blockers, aspirin and metformin have been found to be useful in treating cardiac disease. For better drug delivery, nano therapy is opening new avenues for cardiac research by targeting interleukin (IL), TNF and other proteins by proteome interactome analysis. Nanoparticles enable precise delivery to atherosclerotic plaques, inflammation areas, and damaged cardiac tissues. Advancements in nano therapeutic agents, such as drug-eluting stents and drug-loaded nanoparticles are transforming CVDs management. Plant-based treatments, containing phytochemicals from Botanical sources, have potential cardiovascular benefits. These phytochemicals can mitigate risk factors associated with CVDs. The integration of these strategies opens new avenues for personalized, effective, and minimally invasive cardiovascular care. Altogether, traditional drugs, phytochemicals along with nanoparticles can revolutionize the future cardiac health care by identifying their signaling pathway, mechanism and interactome analysis.

Synergizing drug repurposing and target identification for neurodegenerative diseases.

Despite dedicated research efforts, the absence of disease-curing remedies for neurodegenerative diseases (NDDs) continues to jeopardize human society and stands as a challenge. Drug repurposing is an attempt to find new functionality of existing drugs and take it as an opportunity to discourse the clinically unmet need to treat neurodegeneration. However, despite applying this approach to rediscover a drug, it can also be used to identify the target on which a drug could work. The primary objective of target identification is to unravel all the possibilities of detecting a new drug or repurposing an existing drug. Lately, scientists and researchers have been focusing on specific genes, a particular site in DNA, a protein, or a molecule that might be involved in the pathogenesis of the disease. However, the new era discusses directing the signaling mechanism involved in the disease progression, where receptors, ion channels, enzymes, and other carrier molecules play a huge role. This review aims to highlight how target identification can expedite the whole process of drug repurposing. Here, we first spot various target-identification methods and drug-repositioning studies, including drug-target and structure-based identification studies. Moreover, we emphasize various drug repurposing approaches in NDDs, namely, experimental-based, mechanism-based, and in silico approaches. Later, we draw attention to validation techniques and stress on drugs that are currently undergoing clinical trials in NDDs. Lastly, we underscore the future perspective of synergizing drug repurposing and target identification in NDDs and present an unresolved question to address the issue.

Reimagining old drugs with new tricks: Mechanisms, strategies and notable success stories in drug repurposing for neurological diseases.

Recent evolution in drug repurposing has brought new anticipation, especially in the conflict against neurodegenerative diseases (NDDs). The traditional approach to developing novel drugs for these complex disorders is laborious, time-consuming, and often abortive. However, drug reprofiling which is the implementation of illuminating novel therapeutic applications of existing approved drugs, has shown potential as a promising strategy to accelerate the hunt for therapeutics. The advancement of computational approaches and artificial intelligence has expedited drug repurposing. These progressive technologies have enabled scientists to analyse extensive datasets and predict potential drug-disease interactions. By prospecting into the existing pharmacological knowledge, scientists can recognise potential therapeutic candidates for reprofiling, saving precious time and resources. Preclinical models have also played a pivotal role in this field, confirming the effectiveness and mechanisms of action of repurposed drugs. Several studies have occurred in recent years, including the discovery of available drugs that demonstrate significant protective effects in NDDs, relieve debilitating symptoms, or slow down the progression of the disease. These findings highlight the potential of repurposed drugs to change the landscape of NDD treatment. Here, we present an overview of recent developments and major advances in drug repurposing intending to provide an in-depth analysis of traditional drug discovery and the strategies, approaches and technologies that have contributed to drug repositioning. In addition, this chapter attempts to highlight successful case studies of drug repositioning in various therapeutic areas related to NDDs and explore the clinical trials, challenges and limitations faced by researchers in the field. Finally, the importance of drug repositioning in drug discovery and development and its potential to address discontented medical needs is also highlighted.

Ubiquitin E3 ligases assisted technologies in protein degradation: Sharing pathways in neurodegenerative disorders and cancer.

E3 ligases, essential components of the ubiquitin-proteasome-mediated protein degradation system, play a critical role in cellular regulation. By covalently attaching ubiquitin (Ub) molecules to target proteins, these ligases mark them for degradation, influencing various bioprocesses. With over 600 E3 ligases identified, there is a growing realization of their potential as therapeutic candidates for addressing proteinopathies in cancer and neurodegenerative disorders (NDDs). Recent research has highlighted the need to delve deeper into the intricate roles of E3 ligases as nexus points in the pathogenesis of both cancer and NDDs. Their dysregulation is emerging as a common thread linking these seemingly disparate diseases, necessitating a comprehensive understanding of their molecular intricacies. Herein, we have discussed (i) the fundamental mechanisms through which different types of E3 ligases actively participate in selective protein degradation in cancer and NDDs, followed by an examination of common E3 ligases playing pivotal roles in both situations, emphasising common players. Moving to, (ii) the functional domains and motifs of E3 ligases involved in ubiquitination, we have explored their interactions with specific substrates in NDDs and cancer. Additionally, (iii) we have explored techniques like PROTAC, molecular glues, and other state-of-the-art methods for hijacking neurotoxic and oncoproteins. Lastly, (iv) we have provided insights into ongoing clinical trials, offering a glimpse into the evolving landscape of E3-based therapeutics for cancer and NDDs. Unravelling the intricate network of E3 ligase-mediated regulation holds the key to unlocking targeted therapies that address the specific molecular signatures of individual patients, heralding a new era in personalized medicines.

Triaging between post-translational modification of cell cycle regulators and their therapeutics in neurodegenerative diseases.

Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, present challenges in healthcare because of their complicated etiologies and absence of healing remedies. Lately, the emerging role of post-translational modifications (PTMs), in the context of cell cycle regulators, has garnered big interest as a potential avenue for therapeutic intervention. The review explores the problematic panorama of PTMs on cell cycle regulators and their implications in neurodegenerative diseases. We delve into the dynamic phosphorylation, acetylation, ubiquitination, SUMOylation, Glycation, and Neddylation that modulate the key cell cycle regulators, consisting of cyclins, cyclin-dependent kinases (CDKs), and their inhibitors. The dysregulation of these PTMs is related to aberrant cell cycle in neurons, which is one of the factors involved in neurodegenerative pathologies. Moreover, the effect of exogenous activation of CDKs and CDK inhibitors through PTMs on the signaling cascade was studied in postmitotic conditions of NDDs. Furthermore, the therapeutic implications of CDK inhibitors and associated alteration in PTMs were discussed. Lastly, we explored the putative mechanism of PTMs to restore normal neuronal function that might reverse NDDs.

Emerging trends in post-translational modification: Shedding light on Glioblastoma multiforme.

Recent multi-omics studies, including proteomics, transcriptomics, genomics, and metabolomics have revealed the critical role of post-translational modifications (PTMs) in the progression and pathogenesis of Glioblastoma multiforme (GBM). Further, PTMs alter the oncogenic signaling events and offer a novel avenue in GBM therapeutics research through PTM enzymes as potential biomarkers for drug targeting. In addition, PTMs are critical regulators of chromatin architecture, gene expression, and tumor microenvironment (TME), that play a crucial function in tumorigenesis. Moreover, the implementation of artificial intelligence and machine learning algorithms enhances GBM therapeutics research through the identification of novel PTM enzymes and residues. Herein, we briefly explain the mechanism of protein modifications in GBM etiology, and in altering the biologics of GBM cells through chromatin remodeling, modulation of the TME, and signaling pathways. In addition, we highlighted the importance of PTM enzymes as therapeutic biomarkers and the role of artificial intelligence and machine learning in protein PTM prediction.

New era of artificial intelligence and machine learning-based detection, diagnosis, and therapeutics in Parkinson's disease.

Parkinson's disease (PD) is characterized by the loss of neuronal cells, which leads to synaptic dysfunction and cognitive defects. Despite the advancements in treatment strategies, the management of PD is still a challenging event. Early prediction and diagnosis of PD are of utmost importance for effective management of PD. In addition, the classification of patients with PD as compared to normal healthy individuals also imposes drawbacks in the early diagnosis of PD. To address these challenges, artificial intelligence (AI) and machine learning (ML) models have been implicated in the diagnosis, prediction, and treatment of PD. Recent times have also demonstrated the implication of AI and ML models in the classification of PD based on neuroimaging methods, speech recording, gait abnormalities, and others. Herein, we have briefly discussed the role of AI and ML in the diagnosis, treatment, and identification of novel biomarkers in the progression of PD. We have also highlighted the role of AI and ML in PD management through altered lipidomics and gut-brain axis. We briefly explain the role of early PD detection through AI and ML algorithms based on speech recordings, handwriting patterns, gait abnormalities, and neuroimaging techniques. Further, the review discuss the potential role of the metaverse, the Internet of Things, and electronic health records in the effective management of PD to improve the quality of life. Lastly, we also focused on the implementation of AI and ML-algorithms in neurosurgical process and drug discovery.

Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders.

Neurodegenerative diseases (NDDs) and neuropsychiatric disorders (NPDs) are two common causes of death in elderly people, which includes progressive neuronal cell death and behavioral changes. NDDs include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and motor neuron disease, characterized by cognitive defects and memory impairment, whereas NPDs include depression, seizures, migraine headaches, eating disorders, addictions, palsies, major depressive disorders, anxiety, and schizophrenia, characterized by behavioral changes. Mounting evidence demonstrated that NDDs and NPDs share an overlapping mechanism, which includes post-translational modifications, the microbiota-gut-brain axis, and signaling events. Mounting evidence demonstrated that various drug molecules, namely, natural compounds, repurposed drugs, multitarget directed ligands, and RNAs, have been potentially implemented as therapeutic agents against NDDs and NPDs. Herein, we highlighted the overlapping mechanism, the role of anxiety/stress-releasing factors, cytosol-to-nucleus signaling, and the microbiota-gut-brain axis in the pathophysiology of NDDs and NPDs. We summarize the therapeutic application of natural compounds, repurposed drugs, and multitarget-directed ligands as therapeutic agents. Lastly, we briefly described the application of RNA interferences as therapeutic agents in the pathogenesis of NDDs and NPDs. Neurodegenerative diseases and neuropsychiatric diseases both share a common signaling molecule and molecular phenomenon, namely, pro-inflammatory cytokines, γCaMKII and MAPK/ERK, chemokine receptors, BBB permeability, and the gut-microbiota-brain axis. Studies have demonstrated that any alterations in the signaling mentioned above molecules and molecular phenomena lead to the pathophysiology of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and neuropsychiatric disorders, such as bipolar disorder, schizophrenia, depression, anxiety, autism spectrum disorder, and post-traumatic stress disorder.

Multiple therapeutic approaches of glioblastoma multiforme: From terminal to therapy.

Glioblastoma multiforme (GBM) is an aggressive brain cancer showing poor prognosis. Currently, treatment methods of GBM are limited with adverse outcomes and low survival rate. Thus, advancements in the treatment of GBM are of utmost importance, which can be achieved in recent decades. However, despite aggressive initial treatment, most patients develop recurrent diseases, and the overall survival rate of patients is impossible to achieve. Currently, researchers across the globe target signaling events along with tumor microenvironment (TME) through different drug molecules to inhibit the progression of GBM, but clinically they failed to demonstrate much success. Herein, we discuss the therapeutic targets and signaling cascades along with the role of the organoids model in GBM research. Moreover, we systematically review the traditional and emerging therapeutic strategies in GBM. In addition, we discuss the implications of nanotechnologies, AI, and combinatorial approach to enhance GBM therapeutics.

Glutamatergic neurotransmission: A potential pharmacotherapeutic target for the treatment of cognitive disorders.

In the mammalian brain, glutamate is regarded to be the primary excitatory neurotransmitter due to its widespread distribution and wide range of metabolic functions. Glutamate plays key roles in regulating neurogenesis, synaptogenesis, neurite outgrowth, and neuron survival in the brain. Ionotropic and metabotropic glutamate receptors, neurotransmitters, neurotensin, neurosteroids, and others co-ordinately formulate a complex glutamatergic network in the brain that maintains optimal excitatory neurotransmission. Cognitive activities are potentially synchronized by the glutamatergic activities in the brain via restoring synaptic plasticity. Dysfunctional glutamate receptors and other glutamatergic components are responsible for the aberrant glutamatergic activity in the brain that cause cognitive impairments, loss of synaptic plasticity, and neuronal damage. Thus, controlling the brain's glutamatergic transmission and modifying glutamate receptor function could be a potential therapeutic strategy for cognitive disorders. Certain drugs that regulate glutamate receptor activities have shown therapeutic promise in improving cognitive functions in preclinical and clinical studies. However, several issues regarding precise functional information of glutamatergic activity are yet to be comprehensively understood. The present article discusses the scope of developing glutamatergic systems as prospective pharmacotherapeutic targets to treat cognitive disorders. Special attention has been given to recent developments, challenges, and future prospects.

Unwinding the modalities of necrosome activation and necroptosis machinery in neurological diseases.

Necroptosis, a regulated form of cell death, is involved in the genesis and development of various life-threatening diseases, including cancer, neurological disorders, cardiac myopathy, and diabetes. Necroptosis initiates with the formation and activation of a necrosome complex, which consists of RIPK1, RIPK2, RIPK3, and MLKL. Emerging studies has demonstrated the regulation of the necroptosis cell death pathway through the implication of numerous post-translational modifications, namely ubiquitination, acetylation, methylation, SUMOylation, hydroxylation, and others. In addition, the negative regulation of the necroptosis pathway has been shown to interfere with brain homeostasis through the regulation of axonal degeneration, mitochondrial dynamics, lysosomal defects, and inflammatory response. Necroptosis is controlled by the activity and expression of signaling molecules, namely VEGF/VEGFR, PI3K/Akt/GSK-3ß, c-Jun N-terminal kinases (JNK), ERK/MAPK, and Wnt/ß-catenin. Herein, we briefly discussed the implication and potential of necrosome activation in the pathogenesis and progression of neurological manifestations, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, traumatic brain injury, and others. Further, we present a detailed picture of natural compounds, micro-RNAs, and chemical compounds as therapeutic agents for treating neurological manifestations.

CRISPR/Cas9 gene editing: New hope for Alzheimer's disease therapeutics.

BACKGROUND: Alzheimer's disease (AD) is an insidious, irreversible, and progressive neurodegenerative health condition manifesting as cognitive deficits and amyloid beta (Aß) plaques and neurofibrillary tangles. Approximately 50 million individuals are affected by AD, and the number is rapidly increasing globally. This review explores the role of CRISPR/Cas9 gene editing in the management of AD and its clinical manifestations. AIM OF REVIEW: This review aims to provide a deep insight into the recent progress in CRISPR/Cas9-mediated genome editing and its use against neurodegenerative disorders, specifically AD. However, we have referred to its use against parkinsons's disease (PD), Huntington's disease (HD), and other human diseases, as is one of the most promising and emerging technologies for disease treatment. KEY SCIENTIFIC CONCEPTS OF REVIEW: The pathophysiology of AD is known to be linked with gene mutations, that is, presenilin (PSEN) and amyloid beta precursor protein (APP). However, clinical trials focused at the genetic level could not meet the desired efficiency. The CRISPR/Cas9 genome editing tool is one of the most powerful technologies for correcting inconsistent genetic signatures and now extensively used for AD management. It has significant potential for the correction of undesired gene mutations associated with AD. This technology has allowed the development of empirical AD models, therapeutic lines, and diagnostic approaches for better understanding the nervous system, from in vitro to in vivo models.

Artificial intelligence and machine learning in precision medicine: A paradigm shift in big data analysis.

The integration of artificial intelligence in precision medicine has revolutionized healthcare delivery. Precision medicine identifies the phenotype of particular patients with less-common responses to treatment. Recent studies have demonstrated that translational research exploring the convergence between artificial intelligence and precision medicine will help solve the most difficult challenges facing precision medicine. Here, we discuss different aspects of artificial intelligence in precision medicine that improve healthcare delivery. First, we discuss how artificial intelligence changes the landscape of precision medicine and the evolution of artificial intelligence in precision medicine. Second, we highlight the synergies between artificial intelligence and precision medicine and promises of artificial intelligence and precision medicine in healthcare delivery. Third, we briefly explain the promise of big data analytics and the integration of nanomaterials in precision medicine. Last, we highlight the challenges and opportunities of artificial intelligence in precision medicine.

Cross talk mechanism of disturbed sleep patterns in neurological and psychological disorders.

The incidence and prevalence of sleep disorders continue to increase in the elderly populace, particularly those suffering from neurodegenerative and neuropsychiatric disorders. This not only affects the quality of life but also accelerates the progression of the disease. There are many reasons behind sleep disturbances in such patients, for instance, medication use, nocturia, obesity, environmental factors, nocturnal motor disturbances and depressive symptoms. This review focuses on the mechanism and effects of sleep dysfunction in neurodegenerative and neuropsychiatric disorders. Wherein we discuss disturbed circadian rhythm, signaling cascade and regulation of genes during sleep deprivation. Moreover, we explain the perturbation in brainwaves during disturbed sleep and the ocular perspective of neurodegenerative and neuropsychiatric manifestations in sleep disorders. Further, as the pharmacological approach is often futile and carries side effects, therefore, the non-pharmacological approach opens newer possibilities to treat these disorders and widens the landscape of treatment options for patients.

Protein S-sulfhydration: Unraveling the prospective of hydrogen sulfide in the brain, vasculature and neurological manifestations.

Hydrogen sulfide (H2S) and hydrogen polysulfides (H2Sn) are essential regulatory signaling molecules generated by the entire body, including the central nervous system. Researchers have focused on the classical H2S signaling from the past several decades, whereas the last decade has shown the emergence of H2S-induced protein S-sulfhydration signaling as a potential therapeutic approach. Cysteine S-persulfidation is a critical paradigm of post-translational modification in the process of H2S signaling. Additionally, studies have shown the cross-relationship between S-sulfhydration and other cysteine-induced post-translational modifications, namely nitrosylation and carbonylation. In the central nervous system, S-sulfhydration is involved in the cytoprotection through various signaling pathways, viz. inflammatory response, oxidative stress, endoplasmic reticulum stress, atherosclerosis, thrombosis, and angiogenesis. Further, studies have demonstrated H2S-induced S-sulfhydration in regulating different biological processes, such as mitochondrial integrity, calcium homeostasis, blood-brain permeability, cerebral blood flow, and long-term potentiation. Thus, protein S-sulfhydration becomes a crucial regulatory molecule in cerebrovascular and neurodegenerative diseases. Herein, we first described the generation of intracellular H2S followed by the application of H2S in the regulation of cerebral blood flow and blood-brain permeability. Further, we described the involvement of S-sulfhydration in different biological and cellular functions, such as inflammatory response, mitochondrial integrity, calcium imbalance, and oxidative stress. Moreover, we highlighted the importance of S-sulfhydration in cerebrovascular and neurodegenerative diseases.

Precision Oncology, Signaling, and Anticancer Agents in Cancer Therapeutics.

BACKGROUND: The global alliance for genomics and healthcare facilities provides innovative solutions to expedite research and clinical practices for complex and incurable health conditions. Precision oncology is an emerging field explicitly tailored to facilitate cancer diagnosis, prevention, and treatment based on patients' genetic profiles. Advancements in "omics" techniques, next-generation sequencing, artificial intelligence, and clinical trial designs provide a platform for assessing the efficacy and safety of combination therapies and diagnostic procedures. METHODS: Data were collected from PubMed and Google Scholar using keywords "Precision medicine," "precision medicine and cancer," "anticancer agents in precision medicine," and reviewed comprehensively. RESULTS: Personalized therapeutics, including immunotherapy and cancer vaccines, serve as a groundbreaking solution for cancer treatment. Herein, we take a measurable view of precision therapies and novel diagnostic approaches targeting cancer treatment. The contemporary applications of precision medicine have also been described, along with various hurdles identified in the successful establishment of precision therapeutics. CONCLUSION: This review highlights the key breakthroughs related to immunotherapies, targeted anticancer agents, and target interventions related to cancer signaling mechanisms. The success story of this field in context to drug resistance, safety, patient survival, and improving quality of life is yet to be elucidated. We conclude that, in the near future, the field of individualized treatments may truly revolutionize the nature of cancer patient care.

Free radical biology in neurological manifestations: mechanisms to therapeutics interventions.

Recent advancements and growing attention about free radicals (ROS) and redox signaling enable the scientific fraternity to consider their involvement in the pathophysiology of inflammatory diseases, metabolic disorders, and neurological defects. Free radicals increase the concentration of reactive oxygen and nitrogen species in the biological system through different endogenous sources and thus increased the overall oxidative stress. An increase in oxidative stress causes cell death through different signaling mechanisms such as mitochondrial impairment, cell-cycle arrest, DNA damage response, inflammation, negative regulation of protein, and lipid peroxidation. Thus, an appropriate balance between free radicals and antioxidants becomes crucial to maintain physiological function. Since the 1brain requires high oxygen for its functioning, it is highly vulnerable to free radical generation and enhanced ROS in the brain adversely affects axonal regeneration and synaptic plasticity, which results in neuronal cell death. In addition, increased ROS in the brain alters various signaling pathways such as apoptosis, autophagy, inflammation and microglial activation, DNA damage response, and cell-cycle arrest, leading to memory and learning defects. Mounting evidence suggests the potential involvement of micro-RNAs, circular-RNAs, natural and dietary compounds, synthetic inhibitors, and heat-shock proteins as therapeutic agents to combat neurological diseases. Herein, we explain the mechanism of free radical generation and its role in mitochondrial, protein, and lipid peroxidation biology. Further, we discuss the negative role of free radicals in synaptic plasticity and axonal regeneration through the modulation of various signaling molecules and also in the involvement of free radicals in various neurological diseases and their potential therapeutic approaches. The primary cause of free radical generation is drug overdosing, industrial air pollution, toxic heavy metals, ionizing radiation, smoking, alcohol, pesticides, and ultraviolet radiation. Excessive generation of free radicals inside the cell R1Q1 increases reactive oxygen and nitrogen species, which causes oxidative damage. An increase in oxidative damage alters different cellular pathways and processes such as mitochondrial impairment, DNA damage response, cell cycle arrest, and inflammatory response, leading to pathogenesis and progression of neurodegenerative disease other neurological defects.

Unboxing the molecular modalities of mutagens in cancer.

The etiology of the majority of human cancers is associated with a myriad of environmental causes, including physical, chemical, and biological factors. DNA damage induced by such mutagens is the initial step in the process of carcinogenesis resulting in the accumulation of mutations. Mutational events are considered the major triggers for introducing genetic and epigenetic insults such as DNA crosslinks, single- and double-strand DNA breaks, formation of DNA adducts, mismatched bases, modification in histones, DNA methylation, and microRNA alterations. However, DNA repair mechanisms are devoted to protect the DNA to ensure genetic stability, any aberrations in these calibrated mechanisms provoke cancer occurrence. Comprehensive knowledge of the type of mutagens and carcinogens and the influence of these agents in DNA damage and cancer induction is crucial to develop rational anticancer strategies. This review delineated the molecular mechanism of DNA damage and the repair pathways to provide a deep understanding of the molecular basis of mutagenicity and carcinogenicity. A relationship between DNA adduct formation and cancer incidence has also been summarized. The mechanistic basis of inflammatory response and oxidative damage triggered by mutagens in tumorigenesis has also been highlighted. We elucidated the interesting interplay between DNA damage response and immune system mechanisms. We addressed the current understanding of DNA repair targeted therapies and DNA damaging chemotherapeutic agents for cancer treatment and discussed how antiviral agents, anti-inflammatory drugs, and immunotherapeutic agents combined with traditional approaches lay the foundations for future cancer therapies.

Multifaced role of protein deacetylase sirtuins in neurodegenerative disease.

Sirtuins, a class III histone/protein deacetylase, is a central regulator of metabolic function and cellular stress response. This plays a pivotal role in the pathogenesis and progression of diseases such as cancer, neurodegeneration, metabolic syndromes, and cardiovascular disease. Sirtuins regulate biological and cellular processes, for instance, mitochondrial biogenesis, lipid and fatty acid oxidation, oxidative stress, gene transcriptional activity, apoptosis, inflammatory response, DNA repair mechanism, and autophagic cell degradation, which are known components for the progression of the neurodegenerative diseases (NDDs). Emerging evidence suggests that sirtuins are the useful molecular targets against NDDs like, Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD), and Amyotrophic Lateral Sclerosis (ALS). However, the exact mechanism of neuroprotection mediated through sirtuins remains unsettled. The manipulation of sirtuins activity with its modulators, calorie restriction (CR), and micro RNAs (miR) is a novel therapeutic approach for the treatment of NDDs. Herein, we reviewed the current putative therapeutic role of sirtuins in regulating synaptic plasticity and cognitive functions, which are mediated through the different molecular phenomenon to prevent neurodegeneration. We also explained the implications of sirtuin modulators, and miR based therapies for the treatment of life-threatening NDDs.

Pharmacological intervention in oxidative stress as a therapeutic target in neurological disorders.

OBJECTIVES: Oxidative stress is a major cellular burden that triggers reactive oxygen species (ROS) and antioxidants that modulate signalling mechanisms. Byproducts generated from this process govern the brain pathology and functions in various neurological diseases. As oxidative stress remains the key therapeutic target in neurological disease, it is necessary to explore the multiple routes that can significantly repair the damage caused due to ROS and consequently, neurodegenerative disorders (NDDs). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the critical player of oxidative stress that can also be used as a therapeutic target to combat NDDs. KEY FINDINGS: Several antioxidants signalling pathways are found to be associated with oxidative stress and show a protective effect against stressors by increasing the release of various cytoprotective enzymes and also exert anti-inflammatory response against this oxidative damage. These pathways along with antioxidants and reactive species can be the defined targets to eliminate or reduce the harmful effects of neurological diseases. SUMMARY: Herein, we discussed the underlying mechanism and crucial role of antioxidants in therapeutics together with natural compounds as a pharmacological tool to combat the cellular deformities cascades caused due to oxidative stress.