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Расшифровка Нейропной защиты Bee Venom Peptide Melittin: Insights in Mechanistic Interplay.

Нейродегенеративные заболевания, такие как болезнь Альцгеймера, болезнь Паркинсона и множественный склероз, характеризуются постепенной утратой нейронной структуры и функции. Эти условия часто приводят к когнитивному упадку, дисфункции двигателя и, в конечном счете, к серьезному ухудшению повседневной деятельности. Одной из основных особенностей нейродегенеративных заболеваний является хроническое воспаление, которое приводит к нейронным повреждениям и усугубляет прогрессию заболеваний. Традиционные методы лечения ориентированы главным образом на борьбу с симптомами, а не на устранение коренны

Совпадение в аннотации оригинала
Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, are characterized by progressive loss … eurogenesis. Research indicates that melittin can downregulate pro-apoptotic pathways by inhibiting calpain-mediated activation of apoptosis-inducing factor and Bax, thereby reducing neuronal cell death. Additionally, melittin exerts its neuroprotective effects through the inhibition of neuroinflammatory processes, specifically by downregulating key infla …

An Update on Autophagy as a Target in the Treatment of Alzheimer's Disease.

Proteostasis is crucial for the maintenance and proper operation of cells. Under typical circumstances, the ubiquitin-proteasome system (UPS … I3K/Akt/TSC/mTOR, AMPK/TSC/mTOR, and Rag/mTOR pathways and mTOR-independent ones which include Ca2+/calpain, inositol-dependent, cAMP/EPAC/PLC, and JNK1/Beclin-1/PI3K pathways have been discussed in details. The article sheds light on drugs which are validated with details in tabular form from recent updates in clinical trials.

Inflammation: Roles in Skeletal Muscle Atrophy.

Various diseases can cause skeletal muscle atrophy, usually accompanied by inflammation, mitochondrial dysfunction, apoptosis, decreased protein synthesis, and enhanced proteolysis. The underlying mechanism of inflammation in skeletal muscle atrophy is extremely complex and has not been fully elucidated, thus hindering the development of effective therapeutic drugs and preventive measures for skeletal muscle atrophy. In this review, we elaborate on protein degradation pathways, including the ubiquitin-proteasome system (UPS), the autophagy-lysosome pathway (ALP), the calpain and caspase pathwa…

LRRC8A-dependent volume-regulated anion channels contribute to ischemia-induced brain injury and glutamatergic input to hippocampal neurons.

Volume-regulated anion channels (VRACs) are critically involved in regulating cell volume, and leucine-rich repeat-containing protein 8A (LR … er in Lrrc8a-cKO mice than in WT mice. In addition, MCAO-induced increases in cleaved caspase-3 and calpain activity, two biochemical markers of neuronal apoptosis and death, in brain tissues were significantly attenuated in Lrrc8a-cKO mice compared with WT mice. These new findings indicate that cerebral ischemia increases neuronal LRRC8A-dependent VRAC a …

Epithelial origin of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic, allergen-driven inflammatory disease of the esophagus characterized predominantly by eosinophilic inflammation, leading to esophageal dysfunction. Converging data have placed the esophageal epithelium at the center of disease pathogenesis. In particular, the main EoE disease susceptibility loci at 2p23 and 5p22 encode for gene products that are produced by the esophageal epithelium: the intracellular protease calpain 14 and thymic stromal lymphopoietin, respectively. Furthermore, genetic and functional data establish a primary role for impaired epit…

Synaptophysin depletion and intraneuronal Aβ in organotypic hippocampal slice cultures from huAPP transgenic mice.

BACKGROUND: To date, there are no effective disease-modifying treatments for Alzheimer's disease (AD). In order to develop new therapeutics … laque pathology is not evident even when Aβ1-42 is increased by pharmacological manipulation (using calpain inhibitor 1), indicating that soluble Aβ species, or other APP processing products, are sufficient to cause the initial synaptic changes. CONCLUSIONS: Organotypic brain slices from TgCRND8 mice represent an important new system for understanding me …

Critical role of astrocytic interleukin-17 A in post-stroke survival and neuronal differentiation of neural precursor cells in adult mice.

The brain and the immune system interact in complex ways after ischemic stroke, and the long-term effects of immune response associated with … effect. In addition, after screening for multiple signaling pathways, we revealed that the p38 MAPK/calpain 1 signaling pathway was involved in IL-17 A-mediated neurogenesis in vivo and in vitro. Thus, our results reveal a previously uncharacterized property of astrocytic IL-17 A in the maintenance and augment of survival and neuronal differentiation of N …

Dopaminergic lesioning impairs adult hippocampal neurogenesis by distinct modification of α-synuclein.

Nonmotor symptoms of cognitive and affective nature are present in premotor and motor stages of Parkinson's disease (PD). Neurogenesis, the … pus. Specifically, the presence of truncated α-syn species was accompanied by increased activity of calpain-1, a calcium-dependent protease. Our results further substantiate the broad effects of dopamine loss in PD-susceptible brain nuclei, gradually involved in the PD course. Our findings also indicate a detrimental synergistic interplay between dopamine …

Degenerin channel activation causes caspase-mediated protein degradation and mitochondrial dysfunction in adult C. elegans muscle.

BACKGROUND: Declines in skeletal muscle structure and function are found in various clinical populations, but the intramuscular proteolytic … radation is not suppressed by interventions suppressing proteasome-mediated, autophagy-mediated, or calpain-mediated degradation nor by suppressors of degenerin-induced neurodegeneration. Protein degradation, but not the movement defect, is decreased by treatment with caspase inhibitors or RNAi against ced-3 or ced-4. Adult unc-105 muscles display a time- …

Rapid onset of specific diaphragm weakness in a healthy murine model of ventilator-induced diaphragmatic dysfunction.

BACKGROUND: Controlled mechanical ventilation is associated with ventilator-induced diaphragmatic dysfunction, which impedes weaning from me … e airway pressure groups. No histologic difference was found between groups. In opposition with the calpains, caspase 3 was activated in the mechanical ventilation group. CONCLUSION: Controlled mechanical ventilation for 6 h in the mouse is associated with significant diaphragmatic but not limb muscle weakness without atrophy or sarcolemmal injury and ac …

Phenotypical characteristics, biochemical pathways, molecular targets and putative role of nitric oxide-mediated programmed cell death in Leishmania.

Nitric oxide (NO) has been demonstrated to be the principal effector molecule mediating intracellular killing of Leishmania, both in vitro a … pases and cysteine proteases, in contrast to specific proteasome inhibitors, such as lactacystin or calpain inhibitor I. Moreover, addition of the products of two NO molecular targets, cis-aconitase and glyceraldehyde-3-phosphate dehydrogenase, also had an inhibitory effect on the cell death induced by NO. Interestingly, activities of these two enzymes pl …

White matter injury mechanisms.

White matter of the brain and spinal cord is susceptible to anoxia, ischemia, trauma and autoimmune attack. Irreversible injury to this tiss … elin. Excessive accumulation of cytosolic Ca in turn activates various Ca-dependent enzymes such as calpains, phospholipases and others resulting in irreversible injury. Reoxygenation paradoxically accelerates injury in many axons, and promotes cytoskeletal degradation. Blockers of voltage-gated Na channels represent an attractive therapeutic target becau …

[Molecular and cytometric analysis of renal cell carcinoma cells. Concepts, techniques and prospects].

At the present time, there is no reliable laboratory marker for the diagnosis and prognosis of clear cell renal cell carcinoma (RCC), while … -6, are present in the normal kidney, while others are newly formed antigens (TuM2PK, MN/CA9, CA12, calpain) or ectopic (PSMA, PSA, KLKI, cytokeratin 7 vimentin) or induce abnormal glycosylation (sialyl Lewis'X, galectins) indicating the malignant nature of the cells. The tumour's capacity for progression is related to dysregulations of the cycle (ras, Pa …

Loss-of-function variants in the CAPN1 activator CD99L2 cause X-linked spastic ataxia.

Most patients with a rare movement disorder (MD) do not receive a molecular diagnosis, and the underlying genetic variants and mediating genes remain elusive. Here, we evaluate the diagnostic accuracy of conventional and next-generation sequencing-based genetic testing strategies in a cohort of 2,811 individuals with ataxia, spastic paraplegia and dystonia. Exome sequencing establishes genetic diagnoses in 19.3% of cases, and specificity of phenotypic features and age at testing are positive predictors. Genome analysis 'beyond the exome' increases the diagnostic yield by 7.5%, mostly due to th

Abnormal expression of truncated CRMP-1 protein in the brain cortex of MPSIIIB mice.

Mucopolysaccharidosis IIIB is a lysosomal disease characterized by a severe neurological deterioration, the pathophysiological mechanisms of which are poorly understood. Recently FGF pathway was shown to be altered leading us to explore a downstream target involved in brain development: the collapsin response mediator protein-1 (CRMP-1). CRMP-1 transcript level was normal but a cleavage of CRMP-1 was observed with an abnormal expression of the truncated form until adult age. This truncated CRMP-1 protein could play a role in post-natal cortex maturation and be involved in neuronal alterations

Xiaozheng Anshen Formula alleviates podocyte injury in diabetic kidney disease by restoring autophagy flux via inhibiting TRPC6-mediated calcium signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Emerging evidence implicates podocyte autophagy and calcium channels in diabetic kidney disease (DKD). Xiaoz … SF downregulated TRPC6 expression both in vivo and in vitro, suppressed cytosolic Ca2+ overload and calpain activation, preserved ATG5 and Beclin1, restored autophagic flux, and ultimately protected against podocyte injury and loss. CONCLUSION: XZASF protects podocytes in DKD by restoring impaired autophagy through inhibition of the TRPC6-mediated calciu …

The inhibition mechanism of nanoparticles-loading oxidized hydroxypropyl starch/carrageenan composite films on texture deterioration of chilled beef from the perspective of protein and exudates changes.

In this work, polyphenol nanoparticles-loaded oxidized hydroxypropyl starch/carrageenan (OC/SPH NPs) films were prepared and applied to the … he exudate over extended storage periods. By day 18, the activities of tissue protease B, L, D, and calpain in the exudate reached 25.42 U/g, 33.97 U/g, 0.73 U/g, and 14.29 U/g, respectively. This indicates that the OC/SPH NPs film significantly inhibited the activity of endogenous enzymes in beef, delayed changes in protein oxidation indicators such as s …

New insights in the chronic kidney disease-associated osteoarthritis progression: Role of uremic toxin indoxyl sulfate-induced chondrocyte senescence and ferroptosis.

AIMS: Epidemiological data have shown a notably high co-occurrence of osteoarthritis (OA) and chronic kidney disease (CKD). The pathological … lar iron and calcium, triggering chondrocyte lipid peroxidation, senescence and ferroptosis via the calpain-1/interleukin-1α signaling axis, which could be reversed by both BAPTA and DFO treatment. IS-increased intracellular iron levels could be reversed by DFO, but not BAPTA. In vivo, reducing IS levels with AST-120 or iron chelation with DFO alleviated …

Molecular mechanisms of skeletal muscle atrophy: clinical challenges and future therapeutic strategies.

Skeletal muscle atrophy, characterized by loss of muscle mass and function, is a debilitating feature of chronic diseases, aging, and disuse.It fundamentally results from a sustained imbalance where rates of protein degradation surpass those of synthesis.Key drivers include the hyperactivation of proteolytic systems: the ubiquitin-proteasome system (UPS), autophagy-lysosome pathway (ALP), and calpain/caspase cascades. These systems are regulated by intricate signaling networks. The anabolic insulin-like growth factor 1/phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (I…

CAPNS1 restoration partially alleviates mitochondrial dysfunction and synaptic deficits in Alzheimer's disease through the Ca2+-CaMKIIβ-MAPK-PGC-1α axis.

Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by brain atrophy and cognitive decline. While the amyloid cascade hypothesis remains the dominant framework, accumulating evidence indicates that mitochondrial dysfunction critically contributes to AD progression. Although improving mitochondrial function has been shown to rescue cognitive deficits in AD models, the underlying molecular mechanisms remain elusive. In this study, we identified a significant reduction in calpain small subunit 1 (CAPNS1) expression in both AD patient samples and male transgenic mouse …