Diabetes has been linked to an increased risk of mild cognitive impairment (MCI) a condition characterized by a subtle cognitive decline that may precede the development of dementia. The underlying mechanisms connecting diabetes and MCI involve complex interactions between metabolic dysregulation inflammation and neurodegeneration. A critical mechanism implicated in diabetes and MCI is the activation of inflammatory pathways. Chronic low-grade inflammation as observed in diabetes can lead to the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) interleukin-6 (IL-6) interleukin-1 beta (IL-1β) and interferon-gamma (IFNγ) each of which can exacerbate neuroinflammation and contribute to cognitive decline. A crucial enzyme involved in regulating inflammation is ADAM17 a disintegrin and metalloproteinase which can cleave and release TNF-α from its membrane-bound precursor and cause it to become activated. These processes in turn activate additional inflammation-related pathways such as AKT NF-κB NLP3 MAPK and JAK-STAT pathways. Recent research has provided novel insights into the role of ADAM17 in diabetes and neurodegenerative diseases. ADAM17 is upregulated in both diabetes and Alzheimer's disease suggesting a shared mechanism and implicating inflammation as a possible contributor to much broader forms of pathology and pointing to a possible link between inflammation and the emergence of MCI. This review provides an overview of the different roles of ADAM17 in diabetes-associated mild cognitive impairment diseases. It identifies mechanistic connections through which ADAM17 and associated pathways may influence the emergence of mild cognitive impairment.

Ischemic stroke is a significant cause of morbidity and mortality worldwide. Autophagy a process of intracellular degradation has been shown to play a crucial role in the pathogenesis of ischemic stroke. Long non-coding RNAs (lncRNAs) have emerged as essential regulators of autophagy in various diseases including ischemic stroke. Recent studies have identified several lncRNAs that modulate autophagy in ischemic stroke including MALAT1 MIAT SNHG12 H19 AC136007. 2 C2dat2 MEG3 KCNQ1OT1 SNHG3 and RMRP. These lncRNAs regulate autophagy by interacting with key proteins involved in the autophagic process such as Beclin-1 ATG7 and LC3. Understanding the role of lncRNAs in regulating autophagy in ischemic stroke may provide new insights into the pathogenesis of this disease and identify potential therapeutic targets for its treatment.

Many features of major depressive disorder are mirrored in rodent models of psychological stress. These models have been used to examine the relationship between the activation of the hypothalamic-pituitary axis in response to stress the development of oxidative stress and neuroinflammation the dominance of cholinergic neurotransmission and the associated increase in REM sleep pressure. Rodent models have also provided valuable insights into the impairment of glycolysis and brain glucose utilization by the brain under stress the resulting decrease in brain energy production and the reduction in glutamate/GABA-glutamine cycling. The rapidly acting antidepressants scopolamine ketamine and ECT all raise extracellular glutamate and scopolamine and ketamine have specifically been shown to increase glutamate/GABA-glutamine cycling in men and rodents with corresponding short-term relief of depression. The nightly use of gammahydroxybutyrate (GHB) may achieve more permanent results and may even act prophylactically to prevent the development or recurrence of depression. GHB is a GABAB agonist and restores the normal balance between cholinergic and monoaminergic neurotransmission by inhibiting cholinergic neurotransmission. It relieves REM sleep pressure. GHB’s metabolism generates NADPH a key antioxidant cofactor. Its metabolism also generates succinate the tricarboxylic acid cycle intermediate to provide energy to the cell and to synthesize glutamate. In both animals and man GHB increases the level of brain glutamate.

Central Nervous System (CNS) disorders affect millions of people worldwide with a significant proportion experiencing drug-resistant forms where conventional medications fail to provide adequate seizure control. This abstract delves into recent advancements and innovative therapies aimed at addressing the complex challenge of CNS-related drug-resistant epilepsy (DRE) management. The idea of precision medicine has opened up new avenues for epilepsy treatment. Herbs such as curcumin ginkgo biloba panax ginseng bacopa monnieri ashwagandha and rhodiola rosea influence the BDNF pathway through various mechanisms. These include the activation of CREB inhibition of NF-κB modulation of neurotransmitters reduction of oxidative stress and anti-inflammatory effects. By promoting BDNF expression and activity these herbs support neuroplasticity cognitive function and overall neuronal health. Novel antiepileptic drugs (AEDs) with distinct mechanisms of action demonstrate efficacy in refractory cases where traditional medications falter. Additionally repurposing existing drugs for antiepileptic purposes presents a cost-effective strategy to broaden therapeutic choices. Cannabidiol (CBD) derived from cannabis herbs has garnered attention for its anticonvulsant properties offering a potential adjunctive therapy for refractory seizures. In conclusion recent advances and innovative therapies represent a multifaceted approach to managing drug-resistant epilepsy. Leveraging precision medicine neurostimulation technologies novel pharmaceuticals and complementary therapies clinicians can optimize treatment outcomes and improve the life expectancy of patients living with refractory seizures. Genetic testing and biomarker identification now allow for personalized therapeutic approaches tailored to individual patient profiles. Utilizing next-generation sequencing techniques researchers have elucidated genetic mutations.

Dr. Aloysius Alzheimer a German neuropathologist and psychiatrist recognized the primary instance of Alzheimer's disease (AD) for a millennium and this ailment along with its related dementias remains a severe overall community issue related to health. Nearly fifty million individuals worldwide suffer from dementia with Alzheimer's illness contributing to between 60 and 70% of the instances estimated through the World Health Organization. In addition 82 million individuals are anticipated to be affected by the global dementia epidemic by 2030 and 152 million by 2050. Furthermore age environmental circumstances and inherited variables all increase the likelihood of acquiring neurodegenerative illnesses. Most recent pharmacological treatments are found in original hypotheses of disease which include cholinergic (drugs that show affective cholinergic system availability) as well as amyloid-accumulation (a single drug is an antagonist receptor of N-methyl D-aspartate). In 2020 the FDA provided approval on anti-amyloid drugs. According to mounting scientific data this gut microbiota affects healthy physiological homeostasis and has a role in the etiology of conditions that range between obesity and neurodegenerative disorders like Alzheimer's. The microbiota-gut-brain axis might facilitate interconnection among gut microbes as well as the central nervous system (CNS). Interaction among the microbiota-gut system as well as the brain occurs through the “two-way” microbiota-gut-brain axis. Along this axis the stomach as well as the brain develop physiologically and take on their final forms. This contact is constant and is mediated by numerous microbiota-derived products. The gut microbiota for instance can act as non-genetic markers to set a threshold for maintaining homeostasis or getting ill. The scientific community has conducted research and found that bowel dysbiosis and gastrointestinal tract dysregulation frequently occur in Alzheimer's disease (AD) patients. In this review the effects of the microbiota-gut-brain axis on AD pathogenesis will be discussed.

Although electroconvulsive therapy (ECT) has immediate and profound effects on severe psychiatric disorders compared to pharmacotherapy the mechanisms underlying its therapeutic effects remain elusive. Increasing evidence indicates that glial activation is a common pathogenetic factor in both major depression and schizophrenia raising the question of whether ECT can inhibit glial activation. This article summarizes the findings from both clinical and experimental studies addressing this key question. Based on the findings it is proposed that the suppression of glial activation associated with neuroinflammation may be involved in the mechanism by which ECT restores brain homeostasis and exerts its therapeutic effects.

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that greatly affects the health and life quality of the elderly population. Existing drugs mainly alleviate symptoms but fail to halt disease progression underscoring the urgent need for the development of novel drugs. Based on the neuroprotective effects of flavonoid quercetin in AD this study was designed to identify potential AD-related targets for quercetin and perform in silico prediction of promising analogs for the treatment of AD. Database mining suggested death-associated protein kinase 1 (DAPK1) as the most promising AD-related target for quercetin among seven protein candidates. To achieve better biological effects for the treatment of AD we devised a series of quercetin analogs as ligands for DAPK1 and molecular docking analyses absorption distribution metabolism and excretion (ADME) predictions as well as molecular dynamics (MD) simulations were performed. The energy for drug-protein interaction was predicted and ranked. As a result quercetin-A1a and quercetin-A1a1 out of 19 quercetin analogs exhibited the lowest interaction energy for binding to DAPK1 than quercetin and they had similar dynamics performance with quercetin. In addition quercetin-A1a and quercetin-A1a1 were predicted to have better water solubility. Thus quercetin-A1a and quercetin-A1a1 could be promising agents for the treatment of AD. Our findings paved the way for further experimental studies and the development of novel drugs.