• MeSH
• Central Nervous System growth & development   anatomy & histology   MeSH
• Higher Nervous Activity MeSH
• Publication type
• Conference Proceedings MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• neurovědy

• MeSH
• Immunity, Cellular MeSH
• Child MeSH
• Immunologic Tests MeSH
• Respiratory Tract Infections drug therapy   immunology   MeSH
• Inosine MeSH
• Child, Preschool MeSH
• Check Tag
• Child MeSH
• Child, Preschool MeSH

• MeSH
• Cell Division MeSH
• Epithelium physiology   MeSH
• Hormones physiology   MeSH
• Publication type
• Conference Proceedings MeSH

• Conspectus
• Biochemie. Molekulární biologie. Biofyzika
• NML Fields
• biochemie

• Publication type
• Abstracts MeSH

Mechanismus působení antidepresiv nebyl dosud zcela plně objasněn. Studium vlivu antidepresiv na interakce lipid-protein je nezbytnou součástí výzkumu mimo jiné proto, že plazmatická membrána je prvním místem kontaktu léčiva s cílovou buňkou. Z pohledu membránových hypotéz vzniku depresivní poruchy může být klíčovým mechanismem působení antidepresiv právě buněčná membrána a změny v jejím složení, které se následně promítají do funkce membránově vázaných receptoru, enzymů, přenašečů a iontových kanálů. Jako vhodné modely studia těchto interakcí se používají izolované synapse, krevní buňky, buněčné kultury, izolované buněčné membrány a umělé fosfolipidové membrány.

The mechanisms of antidepressants action that are linked to their therapeutic effects are not sufficiently explained. According to the membrane hypothesis of affective disorders, disturbances in lipid-protein interactions can be predisposing factor in depression and changes in lipid-protein interactions induced by antidepressive drugs can be crucial step in molecular mechanism of their action. The hypothesis is based on well known fact that lipid-protein interactions affect functionality of most membrane integral proteins, including enzymes, receptors, transporters and ion channels ensuring signal transduction. An isolated synapses, blood elements, cell cultures, isolated plasma membranes and artificial phospholipid membranes can be used as proper models.

• MeSH
• Antidepressive Agents pharmacokinetics   pharmacology   MeSH
• Cell Membrane metabolism   drug effects   MeSH
• Molecular Mechanisms of Pharmacological Action MeSH
• Research Support as Topic MeSH
• Financing, Organized MeSH
• Membrane Lipids metabolism   MeSH
• Membrane Proteins drug effects   MeSH
• Synaptosomes drug effects   MeSH

• MeSH
• Cytoplasm MeSH
• Cytoskeleton MeSH
• Cell Membrane Permeability MeSH
• Publication type
• Conference Proceedings MeSH

• Conspectus
• Biochemie. Molekulární biologie. Biofyzika
• NML Fields
• biologie

• MeSH
• Adenosine Triphosphatases MeSH
• Chromatin MeSH
• DNA Helicases * MeSH
• Escherichia coli MeSH
• Genetics * MeSH
• RecQ Helicases MeSH
• Humans MeSH
• Cell Cycle Proteins metabolism   MeSH
• Check Tag
• Humans MeSH

Cellular senescence precipitates a decline in physiological activities and metabolic functions, often accompanied by heightened inflammatory responses, diminished immune function, and impaired tissue and organ performance. Despite extensive research, the mechanisms underpinning cellular senescence remain incompletely elucidated. Emerging evidence implicates circadian rhythm and hypoxia as pivotal factors in cellular senescence. Circadian proteins are central to the molecular mechanism governing circadian rhythm, which regulates homeostasis throughout the body. These proteins mediate responses to hypoxic stress and influence the progression of cellular senescence, with protein Brain and muscle arnt-like 1 (BMAL1 or Arntl) playing a prominent role. Hypoxia-inducible factor-1α (HIF-1α), a key regulator of oxygen homeostasis within the cellular microenvironment, orchestrates the transcription of genes involved in various physiological processes. HIF-1α not only impacts normal circadian rhythm functions but also can induce or inhibit cellular senescence. Notably, HIF-1α may aberrantly interact with BMAL1, forming the HIF-1α-BMAL1 heterodimer, which can instigate multiple physiological dysfunctions. This heterodimer is hypothesized to modulate cellular senescence by affecting the molecular mechanism of circadian rhythm and hypoxia signaling pathways. In this review, we elucidate the intricate relationships among circadian rhythm, hypoxia, and cellular senescence. We synthesize diverse evidence to discuss their underlying mechanisms and identify novel therapeutic targets to address cellular senescence. Additionally, we discuss current challenges and suggest potential directions for future research. This work aims to deepen our understanding of the interplay between circadian rhythm, hypoxia, and cellular senescence, ultimately facilitating the development of therapeutic strategies for aging and related diseases.

• MeSH
• Molecular Targeted Therapy MeSH
• Circadian Rhythm * physiology   MeSH
• Hypoxia-Inducible Factor 1, alpha Subunit metabolism   MeSH
• Cell Hypoxia MeSH
• Hypoxia metabolism   physiopathology   MeSH
• Humans MeSH
• Signal Transduction MeSH
• Cellular Senescence * MeSH
• ARNTL Transcription Factors metabolism   genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Cellular senescence leads to decreased tissue regeneration and inflammation and is associated with diabetes, neurodegenerative diseases, and tumorigenesis. However, the mechanisms of cellular senescence are not fully understood. Emerging evidence has indicated that c-Jun N-terminal kinase (JNK) signaling is involved in the regulation of cellular senescence. JNK can downregulate hypoxia inducible factor-1α to accelerate hypoxia-induced neuronal cell senescence. The activation of JNK inhibits mTOR activity and triggers autophagy, which promotes cellular senescence. JNK can upregulate the expression of p53 and Bcl-2 and accelerates cancer cell senescence; however, this signaling also mediates the expression of amphiregulin and PD-LI to achieve cancer cell immune evasion and prevents their senescence. The activation of JNK further triggers forkhead box O expression and its target gene Jafrac1 to extend the lifespan of Drosophila. JNK can also upregulate the expression of DNA repair protein poly ADP-ribose polymerase 1 and heat shock protein to delay cellular senescence. This review discusses recent advances in understanding the function of JNK signaling in cellular senescence and includes a comprehensive analysis of the molecular mechanisms underlying JNK-mediated senescence evasion and oncogene-induced cellular senescence. We also summarize the research progress in anti-aging agents that target JNK signaling. This study will contribute to a better understanding of the molecular targets of cellular senescence and provides insights into anti-aging, which may be used to develop drugs for the treatment of aging-related diseases.

• MeSH
• Hypoxia MeSH
• JNK Mitogen-Activated Protein Kinases * metabolism   MeSH
• Humans MeSH
• MAP Kinase Signaling System MeSH
• Signal Transduction * MeSH
• Cellular Senescence MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

• MeSH
• Neural Conduction MeSH
• Neurobiology MeSH
• Neurophysiology MeSH
• Neurons physiology   MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• neurologie
• neurovědy