In the case of tauopathies (like Alzheimer's disease), there is a progressive deterioration of neurons in association with abnormal tau hyperphosphorylation followed by destabilization of microtubules and the formation of neurofibrillary tangles. A variety of dysregulated kinase signaling pathways have been heavily implicated in the regulation of tau phosphorylation and disease progression, such as those involving glycogen synthase kinase 3β (GSK 3β), cyclin dependent kinase 5 (CDK5) and mitogen activated protein kinases (MAPKs). In this context, the MAPK/ERK signaling pathway, in particular ERK1/2, has been identified as a key pathway involved in regulating tau-associated processes, neuronal plasticity and survival and is of particular interest in Tau mediated neurodegeneration. In this review, the molecular mechanisms and the connection between kinase regulation, synaptic dysfunction and tau pathology are discussed, especially with regard to ERK1/2-mediated signaling. Previous studies have shown that HEK1/2 modulation can be implicated in tau phosphorylation pathways and has implications as a therapeutic target. Further, preclinical studies using natural compounds like Baicalein have been conducted to show their possible neuroprotective effects, but they need to be further tested in experiments to confirm their efficacy, target engagement and therapeutic relevance in tauopathies. In general, this review emphasizes the roles of kinase signaling pathways in tau mediated neurodegeneration and suggests ERK1/2 as an interesting therapeutic target. Additional in vitro, in vivo and clinical research is needed to assess the translatability of ERK1/2 targeting strategies for disease modifying treatment in tauopathies.
Shravya Sharma, Manisha Singh· BIO Web of Conferences· 0 citations
Oral cancer represents a major public health challenge in India accounting for significant mortality globally. It is among the most common cancers in the south-east asia, due to prevalent tobacco use and betel-quid chewing. Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity, accounting for most of oral cancers. Salvia officinalis L. (common sage) has long been valued in traditional healing systems for its pharmacological potential. The bioactivity of Salvia officinalis is due to its diverse profile of phytochemicals, such as rosmarinic acid, carnosic acid, carnosol, terpenoids and flavonoids. Preliminary findings suggest that Sage extracts act through inhibition of proinflammatory NF-?B signaling pathways and regulation of MAPK/ERK signaling cascades involved in tumor progression. These are also involved in scavenging of reactive oxygen species (ROS) to protect cells from oxidative cellular damage leading to apoptosis by modulating mitochondrial associated pathways. Sage extracts report significantly reduced viability of human carcinoma cells, altering the expression of genes regulating cell cycle control, DNA repair, and p53 signaling, suggesting activation of tumor-suppressive pathways. One of the major bioactive compounds in sage, rosmarinic acid, has been shown to suppress proliferation of oral cancer cells, by inducing G2/M cell-cycle arrest, trigger endoplasmic reticulum stress, and promote apoptosis, while also reducing their migratory capacity. Present investigations further indicate that sage preparations may offer therapeutic benefits in managing inflammatory and other metabolic disorders related to OSCC and are generally safe for human use. Overall, these findings highlight Salvia officinalis as a scientifically relevant medicinal resource rich in bioactive phytochemicals for management of OSCC. Further research, particularly mechanistic investigations and in vivo validation, is required to establish its clinical efficacy and safety.
P. Saxena, M. Haque, N. Mishra et al.· Medicinal Plants - Internati...· 0 citations
Alzheimer’s disease (AD) is marked by progressive neuronal deterioration resulting from the convergence of mitochondrial dysfunction, disrupted iron homeostasis, elevated oxidative stress, and compromised cellular quality-control systems. In addition to the well-established roles of amyloid-a accumulation and tau pathology, mounting evidence implicates ferroptosis- an iron-dependent, lipid peroxidation-driven mode of regulated cell death-together with defects in autophagy and mitophagy, as tightly interconnected contributors to neuronal degeneration. Despite increasing recognition of this pathological interplay, therapeutic approaches capable of concurrently targeting these mechanisms remain scarce. Berberine, a naturally occurring isoquinoline alkaloid, has attracted interest as a pleiotropic compound with reported antioxidant, mitochondria-stabilizing, and autophagy-modulatory activities. In the present study, a computational systems biology approach was employed to investigate the interplay between ferroptosis, autophagy, and mitophagy in Alzheimer’s disease. Differentially expressed genes were integrated with curated pathway-specific gene sets to identify key overlapping regulators within the FMA axis. Functional enrichment and network-level analyses revealed that these genes are involved in pathways associated with oxidative stress, mitochondrial quality control, and impaired proteostasis. Furthermore, molecular docking analysis suggested that berberine exhibits favourable binding interactions with selected hub targets, supporting its potential role in modulating interconnected cell death and survival pathways. Collectively, these findings highlight the coordinated dysregulation of the FMA axis in AD and provide a computational basis for exploring multi-target therapeutic strategies.
