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Документ Hereditary spastic paraplegia: Novel insights into the pathogenesis and management(SAGE, 2024-01) Awuah, Wireko Andrew; Tan, Joecelyn Kirani; Shkodina, Anastasiia D; Ferreira, Tomas; Adebusoye, Favour Tope; Mazzoleni, Adele; Wellington, Jack; David, Lian; Chilcott, Ellie; Huang, Helen; Abdul-Rahman, Toufik; Shet, Vallabh; Atallah, Oday; Kalmanovich, Jacob; Jiffry, Riaz; Madhu, Divine Elizabeth; Sikora, Kateryna; Kmyta, Oleksii; Delva, Mykhailo Yu.; Шкодіна, Анастасія Дмитрівна; Дельва, Михайло ЮрійовичHereditary spastic paraplegia is a genetically heterogeneous neurodegenerative disorder characterised primarily by muscle stiffness in the lower limbs. Neurodegenerative disorders are conditions that result from cellular and metabolic abnormalities, many of which have strong genetic ties. While ageing is a known contributor to these changes, certain neurodegenerative disorders can manifest early in life, progressively affecting a person’s quality of life. Hereditary spastic paraplegia is one such condition that can appear in individuals of any age. In hereditary spastic paraplegia, a distinctive feature is the degeneration of long nerve fibres in the corticospinal tract of the lower limbs. This degeneration is linked to various cellular and metabolic processes, including mitochondrial dysfunction, remodelling of the endoplasmic reticulum membrane, autophagy, abnormal myelination processes and alterations in lipid metabolism. Additionally, hereditary spastic paraplegia affects processes like endosome membrane trafficking, oxidative stress and mitochondrial DNA polymorphisms. Disease-causing genetic loci and associated genes influence the progression and severity of hereditary spastic paraplegia, potentially affecting various cellular and metabolic functions. Although hereditary spastic paraplegia does not reduce a person’s lifespan, it significantly impairs their quality of life as they age, particularly with more severe symptoms. Regrettably, there are currently no treatments available to halt or reverse the pathological progression of hereditary spastic paraplegia. This review aims to explore the metabolic mechanisms underlying the pathophysiology of hereditary spastic paraplegia, emphasising the interactions of various genes identified in recent network studies. By comprehending these associations, targeted molecular therapies that address these biochemical processes can be developed to enhance treatment strategies for hereditary spastic paraplegia and guide clinical practice effectively.Документ Immunological and inflammatory effects of infectious diseases in circadian rhythm disruption and future therapeutic directions(Springer, 2023-01-19) Huang, Helen; Mehta, Aashna; Jacob, Kalmanovich; Anand, Ayush; Bejarano, Maria Chilo; Garg, Tulika; Khan, Nida; Тonpouwo, Gauvain Kankeu; Shkodina, Anastasiia D.; Bardhan, Mainak; Шкодіна, Анастасія ДмитрівнаBackground Circadian rhythm is characterised by daily variations in biological activity to align with the light and dark cycle. These diurnal variations, in turn, influence physiological functions such as blood pressure, temperature, and sleep–wake cycle. Though it is well established that the circadian pathway is linked to pro-inflammatory responses and circulating immune cells, its association with infectious diseases is widely unknown. Objective This comprehensive review aims to describe the association between circadian rhythm and host immune response to various kinds of infection. Methods We conducted a literature search in databases Pubmed/Medline and Science direct. Our paper includes a comprehensive analysis of findings from articles in English which was related to our hypothesis. Findings Molecular clocks determine circadian rhythm disruption in response to infection, influencing the host’s response toward infection. Moreover, there is a complex interplay with intrinsic oscillators of pathogens and the influence of specific infectious processes on the CLOCK: BMAL1 pathway. Such mechanisms vary for bacterial and viral infections, both well studied in the literature. However, less is known about the association of parasitic infections and fungal pathogens with circadian rhythm modulation. Conclusion It is shown that bidirectional relationships exist between circadian rhythm disruption and infectious process, which contains interplay between the host’s and pathogens’ circadian oscillator, immune response, and the influence of specific infectious. Further studies exploring the modulations of circadian rhythm and immunity can offer novel explanations of different susceptibilities to infection and can lead to therapeutic avenues in circadian immune modulation of infectious diseases.