Sub-cellular biochemistry最新文献

Ageing is generally characterised by the declining ability to respond to stress, increasing homeostatic imbalance, and increased risk of ageing-associated diseases . Mechanistically, the lifelong accumulation of a wide range of molecular and cellular impairments leads to organismal senescence. The aging population poses a severe medical concern due to the burden it places on healthcare systems and the general public as well as the prevalence of diseases and impairments associated with old age. In this chapter, we discuss organ failure during ageing as well as ageing of the hypothalamic-pituitary-adrenal axis and drugs that can regulate it. A much-debated subject is about ageing and regeneration. With age, there is a gradual decline in the regenerative properties of most tissues. The goal of regenerative medicine is to restore cells, tissues, and structures that are lost or damaged after disease, injury, or ageing. The question arises as to whether this is due to the intrinsic ageing of stem cells or, rather, to the impairment of stem-cell function in the aged tissue environment. The risk of having a stroke event doubles each decade after the age of 55. Therefore, it is of great interest to develop neurorestorative therapies for stroke which occurs mostly in elderly people. Initial enthusiasm for stimulating restorative processes in the ischaemic brain with cell-based therapies has meanwhile converted into a more balanced view, recognising impediments related to survival, migration, differentiation, and integration of therapeutic cells in the hostile aged brain environment. Therefore, a current lack of understanding of the fate of transplanted cells means that the safety of cell therapy in stroke patients is still unproven. Another issue associated with ischaemic stroke is that patients at risk for these sequels of stroke are not duly diagnosed and treated due to the lack of reliable biomarkers. However, recently neurovascular unit-derived exosomes in response to Stroke and released into serum are new plasma genetic and proteomic biomarkers associated with ischaemic stroke. The second valid option, which is also more economical, is to invest in prevention.

Age-related chronic inflammation is characterized as the unresolved low-grade inflammatory process underlying the ageing process and various age-related diseases. In this chapter, we review the age-related changes in the oxidative stress-sensitive pro-inflammatory NF-κB signaling pathways causally linked with chronic inflammation during ageing based on senoinflammation schema. We describe various age-related dysregulated pro- and anti-inflammatory cytokines, chemokines, and senescence-associated secretory phenotype (SASP), and alterations of inflammasome, specialized pro-resolving lipid mediators (SPM), and autophagy as major players in the chronic inflammatory intracellular signaling network. A better understanding of the molecular, cellular, and systemic mechanisms involved in chronic inflammation in the ageing process would provide further insights into the potential anti-inflammatory strategies.

Age-related hearing loss (ARHL), or presbycusis, occurs in most mammals, humans included, with a different age of onset and magnitude of loss. It is associated with two major symptoms: loss of sensitivity to sound, especially for high pitches, and a reduced ability to understand speech in background noise. This phenomenon involves both the peripheral structures of the inner ear and the central acoustic pathways. Several mechanisms have been identified as pro-ageing in the human cochlea. The main one is the oxidative stress. The inner ear physiological degeneration can be affected by both intrinsic conditions, such as genetic predisposition, and extrinsic ones, such as noise exposure. The magnitude of neuronal loss precedes and exceeds that of inner hair cell loss, which is also less important than the loss of outer hair cells. Patients with HL often develop atrophy of the temporal lobe (auditory cortex) and brain gliosis can contribute to the development of a central hearing loss. The presence of white matter hyperintensities (WMHs) on the MRI, which is radiologic representation of brain gliosis, can justify a central HL due to demyelination in the superior auditory pathways. Recently, the presence of WMHs has been correlated with the inability to correctly understand words in elderly with normal auditory thresholds.

The progression of age triggers a vast number of diseases including cardiovascular, cancer, and neurodegenerative disorders. Regardless of our plentiful knowledge about age-related diseases, little is understood about molecular pathways that associate the ageing process with various diseases. Several cellular events like senescence, telomere dysfunction, alterations in protein processing, and regulation of gene expression are common between ageing and associated diseases. Accumulating information on the role of microRNAs (miRNAs) suggests targeting miRNAs can aid our understanding of the interplay between ageing and associated diseases. In the present chapter, we have attempted to explore the information available on the role of miRNAs in ageing of various tissues/organs and diseases and understand the molecular mechanism of ageing.

The cytoskeleton, which includes actin filaments, microtubules, and intermediate filaments, is one of the most important networks in the cell and undertakes many fundamental life activities. Among them, actin filaments are mainly responsible for maintaining cell shape and mediating cell movement, microtubules are in charge of coordinating all cargo transport within the cell, and intermediate filaments are mainly thought to guard against external mechanical pressure. In addition to this, cytoskeleton networks are also found to play an essential role in multiple viral infections. Due to the COVID-19 epidemic, including SARS-CoV-2, SARS-CoV and MERS-CoV, so many variants have caused wide public concern, that any virus infection can potentially bring great harm to human beings and society. Therefore, it is of great importance to study coronavirus infection and develop antiviral drugs and vaccines. In this chapter, we summarize in detail how the cytoskeleton responds and participates in coronavirus infection by analyzing the possibility of the cytoskeleton and its related proteins as antiviral targets, thereby providing ideas for finding more effective treatments.

RNA virus infections have been a leading cause of pandemics. Aided by global warming and increased connectivity, their threat is likely to increase over time. The flaviviruses are one such RNA virus family, and its prototypes such as the Japanese encephalitis virus (JEV), Dengue virus, Zika virus, West Nile virus, etc., pose a significant health burden on several endemic countries. All viruses start off their life cycle with an infected cell, wherein a series of events are set in motion as the virus and host battle for autonomy. With their remarkable capacity to hijack cellular systems and, subvert/escape defence pathways, viruses are able to establish infection and disseminate in the body, causing disease. Using this strategy, JEV replicates and spreads through several cell types such as epithelial cells, fibroblasts, monocytes and macrophages, and ultimately breaches the blood-brain barrier to infect neurons and microglia. The neurotropic nature of JEV, its high burden on the paediatric population, and its lack of any specific antivirals/treatment strategies emphasise the need for biomedical research-driven solutions. Here, we highlight the latest research developments on Japanese encephalitis virus-infected cells and discuss how these can aid in the development of future therapies.

Novel imaging technologies such as single-particle tracking provide tools to study the intricate process of virus infection in host cells. In this chapter, we provide an overview of studies in which single-particle tracking technologies were applied for the analysis of the viral entry pathways in the context of the live host cell. Single-particle tracking techniques have been dependent on advances in the fluorescent labeling microscopy method and image analysis. The mechanistic and kinetic insights offered by this technique will provide a better understanding of virus entry and may lead to a rational design of antiviral interventions.

Tendons are mechanosensitive connective tissues responsible for the connection between muscles and bones by transmitting forces that allow the movement of the body, yet, with advancing age, tendons become more prone to degeneration followed by injuries. Tendon diseases are one of the main causes of incapacity worldwide, leading to changes in tendon composition, structure, and biomechanical properties, as well as a decline in regenerative potential. There is still a great lack of knowledge regarding tendon cellular and molecular biology, interplay between biochemistry and biomechanics, and the complex pathomechanisms involved in tendon diseases. Consequently, this reflects a huge need for basic and clinical research to better elucidate the nature of healthy tendon tissue and also tendon aging process and associated diseases. This chapter concisely describes the effects that the aging process has on tendons at the tissue, cellular, and molecular levels and briefly reviews potential biological predictors of tendon aging. Recent research findings that are herein reviewed and discussed might contribute to the development of precision tendon therapies targeting the elderly population.

The vertebrate nervous system is divided into central (CNS) and peripheral (PNS) components. In turn, the PNS is divided into the autonomic (ANS) and enteric (ENS) nervous systems. Ageing implicates time-related changes to anatomy and physiology in reducing organismal fitness. In the case of the CNS, there exists substantial experimental evidence of the effects of age on individual neuronal and glial function. Although many such changes have yet to be experimentally observed in the PNS, there is considerable evidence of the role of ageing in the decline of ANS function over time. As such, this chapter will argue that the ANS constitutes a paradigm for the physiological consequences of ageing, as well as for their clinical implications.

The UCS (UNC-45/CRO1/She4p) family of proteins has emerged as chaperones specific for the folding, assembly, and function of myosin. UCS proteins participate in various myosin-dependent cellular processes including myofibril organization and muscle functions, cell differentiation, striated muscle development, cytokinesis, and endocytosis. Mutations in the genes that code for UCS proteins cause serious defects in myosin-dependent cellular processes. UCS proteins that contain an N-terminal tetratricopeptide repeat (TPR) domain are called UNC-45. Vertebrates usually possess two variants of UNC-45, the ubiquitous general-cell UNC-45 (UNC-45A) and the striated muscle UNC-45 (UNC-45B), which is exclusively expressed in skeletal and cardiac muscles. Except for the TPR domain in UNC-45, UCS proteins comprise of several irregular armadillo (ARM) repeats that are organized into a central domain, a neck region, and the canonical C-terminal UCS domain that functions as the chaperoning module. With or without TPR, UCS proteins form linear oligomers that serve as scaffolds that mediate myosin folding, organization into myofibrils, repair, and motility. This chapter reviews emerging functions of these proteins with a focus on UNC-45 as a dedicated chaperone for folding, assembly, and function of myosin at protein and potentially gene levels. Recent experimental evidences strongly support UNC-45 as an absolute regulator of myosin, with each domain of the chaperone playing different but complementary roles during the folding, assembly, and function of myosin, as well as recruiting Hsp90 as a co-chaperone to optimize key steps. It is becoming increasingly clear that UNC-45 also regulates the transcription of several genes involved in myosin-dependent cellular processes.