Current Drug Targets - Online First
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Lipidomics in Breast Cancer: Decoding Metabolic Reprogramming and Unlocking Therapeutic Opportunities
Authors: Harshita Singhai, Sunny Rathee and Umesh K. PatilAvailable online: 24 June 2025More LessLipidomics, a cutting-edge branch of metabolomics provides a comprehensive understanding of the lipidome and its alterations in cellular and systemic processes. In Breast Cancer (BC), a highly heterogeneous disease, lipidomics has emerged as a pivotal tool for exploring metabolic reprogramming, tumor progression, and therapeutic resistance. This review highlights the intricate relationship between lipid metabolism and breast cancer, with a focus on subtype-specific lipid dependencies, oxidative stress, and ferroptosis. Technological advancements, such as mass spectrometry and chromatography, have enabled precise profiling of lipid alterations, revealing distinct lipid signatures across breast cancer subtypes. Key enzymes like acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN), along with lipid regulators like PPARγ, have been identified as central players in lipid-driven tumorigenesis. Lipidomic studies offer the potential for biomarker discovery and the development of lipid-targeted therapies. Despite challenges in standardization and integration with other omics approaches, lipidomics is poised to revolutionize breast cancer diagnostics and therapeutics, providing novel insights into the metabolic underpinnings of this complex disease.
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Advancing myloid ggregation esearch: ocus n nnovative Therapies, Molecular Modeling and Nano-Delivery Systems in Alzheimer’s Disease
Authors: Umaira Hasan, Himangini Jain and Ruhi AliAvailable online: 24 June 2025More LessIntroductionAlzheimer’s disease (AD), the most common form of dementia, is a major global health issue. Its complex pathology, including amyloid-beta (Aβ) aggregation, leads to neuronal damage and cognitive decline. Since Aβ plays a major role in AD, therapies targeting its production, aggregation, and clearance are being actively explored. This review discusses recent advances in gene therapy, enzyme inhibitors, molecular modeling, and nano-delivery systems aimed at modifying AD progression, highlighting their potential and challenges.
MethodsThis review compiles findings on BACE1 and γ-secretase inhibitors, gene therapies that modify amyloid metabolism, and combination therapies. Studies have been selected based on their focus on Aβ regulation and their impact on disease progression, cognitive function, and breakthroughs in diagnostics, molecular modeling, and drug delivery for neurodegenerative conditions.
ResultsBACE1 inhibitors, such as verubecestat, and γ-secretase inhibitors, shows potential, however, they face significant challenges related to BBB penetration and adverse effects. Gene therapies using AAV vectors and CRISPR/Cas9 technologies are promising, particularly for individuals genetically predisposed to these diseases. Combination therapies targeting amyloid, tau, and neuro-inflammation have emerged as effective approaches. Advancements in PET, SPECT, MRI, small molecule probes, molecular modeling, and nano-particle-based drug delivery are improving diagnostic and treatment options.
DiscussionThe findings emphasize the multifactorial complexity of amyloid disorders and the limitations of mono-therapies. While certain agents demonstrated efficacy in early disease stages, most treatments have failed in advanced phases due to poor central nervous system (CNS) bioavailability, adverse effects, or insufficient target engagement. Novel delivery systems, combination therapies, and computational design approaches offer enhanced translational potential. However, challenges such as immune responses, delivery efficiency, and off-target effects continue to pose significant barriers.
ConclusionAβ-targeted therapies, including enzyme inhibitors and gene therapies, hold promise, though challenges such as BBB penetration and toxicity still remain. Combination therapies, along with advancements in diagnostics and drug delivery technology, are essential for finding effective treatments for Alzheimer’s, Parkinson’s, and other neurodegenerative diseases. Future research should prioritize overcoming the persistent barriers to BBB penetration, enhancing therapeutic selectivity, and refining drug delivery systems to enable more precise, targeted interventions, to ultimately reduce the progression of disease at the molecular level.
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Neurostimulation for the Management of Epilepsy: Advances in Targeted Therapy
Available online: 27 May 2025More LessBackgroundEpilepsy is a multifaceted neurological disorder marked by seizures that can present with a wide range of symptoms. Despite the prevalent use of anti-epileptic drugs, drug resistance and adverse effects present considerable obstacles. Despite advancements in anti-epileptic drugs (AEDs), approximately 20-30% of patients remain drug-resistant, highlighting the need for innovative therapeutic strategies.
AimThis study aimed to explore advancements in epilepsy diagnosis and treatment utilizing modern technology and medicines.
MethodsThe literature survey was carried out using Scopus, ScienceDirect, and Google Scholar. Data from the last 10 years were preferred to include in the study.
ResultEmerging technologies, such as artificial intelligence, gene therapy, and wearable gadgets, have transformed epilepsy care. EEG and MRI play essential roles in diagnosis, while AI aids in evaluating big datasets for more accurate seizure identification. Machine learning and artificial intelligence are increasingly integrated into diagnostic processes to enhance seizure detection and classification. Wearable technology improves patient self-monitoring and helps clinical research. Furthermore, gene treatments offer promise by treating the fundamental causes of seizure activity, while stem cell therapies give neuroprotective and regenerative advantages. Dietary interventions, including ketogenic diets, are being examined for their ability to modify neurochemical pathways implicated in epilepsy.
ConclusionRecent technological and therapeutic developments provide major benefits in epilepsy assessment and treatment, with AI and wearable devices enhancing seizure detection and patient monitoring. Nonetheless, additional study is essential to ensure greater clinical application and efficacy. Future perspectives include the potential of optogenetics and advanced signal processing techniques to revolutionize treatment paradigms, emphasizing the importance of personalized medicine in epilepsy care. Overall, a comprehensive understanding of the multifaceted nature of epilepsy is essential for developing effective interventions and improving patient outcomes.
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RAAS Overactivation and Mitochondrial Damage Signaling as Key Players in Lethal COVID-19
Authors: Sabrina Fulkerson, Grace Hohman, Tyler Stark, Selman Aydogdu and Mohamed EldeebAvailable online: 27 May 2025More LessCoronavirus disease 2019 (COVID-19), which led to a global pandemic causing millions of deaths, is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). While previous research on COVID-19 has primarily utilized nasal swabs and blood samples, these do not provide comprehensive insights into all the organ systems affected by the infection. A recent study by Topper et al. addressed this gap by analyzing both nasal samples and autopsy tissues from SARS-CoV-2-infected individuals. Their findings highlight a significant role of mitochondrial damage pathways and RAAS overactivation in contributing to the severity of SARS- CoV-2 infections. Importantly, targeting mitochondrial dysfunction and RAAS overactivation pathways may offer promising and specific druggable targets for treating COVID-19 patients.
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Therapeutic Aspects of Melatonin-sirtuin Crosstalk: An Updated Review of Current Data Based on Cellular Mechanisms
Available online: 14 May 2025More LessMelatonin, a master regulator of circadian rhythms and diverse physiological processes, exhibits complex interactions with various molecules. Sirtuins, a family of histone deacetylases, are key players in aging, stress responses, and metabolism and represent a critical target for melatonin. This review explores the multifaceted functions of melatonin and sirtuins, delving into the molecular mechanisms of their interaction. We further examine the impact of this synergy on various pathologies across different organs. Studies suggest that melatonin modulates SIRT1 and SIRT3 signaling pathways, offering protection in neurodegenerative, cardiovascular, skeletal, and pulmonary diseases, as well as renal and hepatic dysfunction. Additionally, melatonin-sirtuin interactions have been implicated in mitigating cancer development and promoting health in the female and male reproductive systems. Notably, the majority of studies across these systems demonstrate melatonin's ability to regulate SIRT1 and SIRT3 signaling, thereby alleviating associated pathologies. In conclusion, the intricate interplay between melatonin and, particularly, SIRT1 and SIRT3 emerges as a crucial modulator of diverse signaling pathways, with promising therapeutic implications for a wide range of diseases.
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IL-17 Antagonists as a Promising Therapeutic Modality for Hidradenitis Suppurativa
Authors: Piotr K. Krajewski and Jacek C. SzepietowskiAvailable online: 30 April 2025More LessHidradenitis suppurativa (HS) is an inflammatory, debilitating skin disorder affecting primarily young adults [1]. The course of the disease is chronic, with recurrent flares of inflammatory nodules, abscesses, and inflammatory tunnels localized mainly in the intertriginous areas [1]. It has been studied that HS, characterized by a high severity of pain and constant purulent discharge, has an enormous impact on a patient’s quality of life and is often associated with depression, anxiety, stigmatization, workplace challenges, and suicidal ideations [2, 3]. Due to the unknown pathogenesis and HS’s multifactorial nature, the treatment is difficult and often unsatisfactory for clinicians and patients [1, 4].
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Microwave-assisted Green Synthesis: An Approach for the Development of Anti-tubercular Agents
Available online: 23 April 2025More LessTuberculosis (TB) is a serious infectious disease that primarily affects the lungs but can also spread to the brain and spine. The highly pathogenic bacteria that causes TB is called Mycobacterium tuberculosis (Mtb). Usually, when an infected person coughs, sneezes, or speaks, the disease spreads through the air. TB is treatable with antibiotics, but it requires a long course of treatment, usually 6 to 9 months to eliminate the bacteria and prevent drug resistance. Thus, developing novel anti-tubercular therapeutics with various structural classes is necessary to solve the problems brought on by strains that are resistant to several currently available therapies.
Resistance to widely used anti-tubercular drugs is increasing daily. As a result, continuing medication therapy is necessary to stop more microbial infections. However, it leads to treatment resistance, which increases the likelihood that the disease may resurface in immune-compromised patients. Several anti-tubercular medications with various molecular structures show appropriate anti-tubercular action against Mycobacterium TB strains that are drug-sensitive and drug-resistant. Compared to conventional synthetic methods, synthetic reactions can be carried out more effectively and selectively under simple reaction conditions by employing microwave radiation. Microwave-assisted organic synthesis (MAOS) is a useful method for increasing product yield and selectivity while accelerating the reaction rate for different types of organic synthesis. Several lead compounds with anti-tubercular properties that were synthesized using the microwave irradiation (MWI) approach are discussed in the current work.
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Emerging Carbon Dots Nanomaterials for Ovarian Cancer Diagnosis and Therapy
Available online: 04 February 2025More LessDelayed diagnosis and limited treatment options make ovarian cancer difficult to treat. This paper examines the growing role of Carbon Dots (CDs) in ovarian cancer diagnosis and treatment. Photoluminescence and biocompatibility make CDs ideal for biomedical use. We emphasize their ability to improve fluorescence and molecular imaging in imaging and diagnostics. We also demonstrate the efficacy of carbon dots in targeted drug delivery systems in overcoming drug resistance and improving therapeutic outcomes. Photodynamic and photothermal therapies are used to show that CDs can treat hypoxic ovarian cancer tumours. We also discuss CD safety issues and constraints, emphasising the need for thorough assessments and fine-tuning. Future research focuses on personalised medicine and CD integration with other therapies. This text concludes by discussing CDs' clinical use and the challenges of production and regulatory approval. CDs can improve ovarian cancer diagnosis and treatment, improving patient outcomes and survival.
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