1.
2.
Blomgren, Klas, 1963, et al.
(författare)
Pathological apoptosis in the developing brain
2007
Ingår i: Apoptosis. - : Springer Science and Business Media LLC. - 1360-8185 .- 1573-675X. ; 12:5, s. 993-1010
Forskningsöversikt (refereegranskat) abstract
More than half of the initially-formed neurons are deleted in certain brain regions during normal development. This process, whereby cells are discretely removed without interfering with the further development of remaining cells, is called programmed cell death (PCD). The term apoptosis is used to describe certain morphological manifestations of PCD. Many of the effectors of this developmental cell death program are highly expressed in the developing brain, making it more susceptible to accidental activation of the death machinery, e.g. following hypoxia-ischemia or irradiation. Recent evidence suggests, however, that activation and regulation of cell death mechanisms under pathological conditions do not exactly mirror physiological, developmentally regulated PCD. It may be argued that the conditions after e.g. ischemia are not even compatible with the execution of PCD as we know it. Under pathological conditions cells are exposed to various stressors, including energy failure, oxidative stress and unbalanced ion fluxes. This results in parallel triggering and potential overshooting of several different cell death pathways, which then interact with one another and result in complex patterns of biochemical manifestations and cellular morphological features. These types of cell death are here called "pathological apoptosis," where classical hallmarks of PCD, like pyknosis, nuclear condensation and caspase-3 activation, are combined with non-PCD features of cell death. Here we review our current knowledge of the mechanisms involved, with special focus on the potential for therapeutic intervention tailored to the needs of the developing brain.
3.
Ekström, Per A R, et al.
(författare)
Impaired nerve regeneration in streptozotocin-diabetic rats. Effects of treatment with an aldose reductase inhibitor
1989
Ingår i: Journal of the Neurological Sciences. - 0022-510X. ; 93:2-3, s. 231-237
Forskningsöversikt (refereegranskat) abstract
Rats with streptozotocin-induced diabetes have a decreased rate of sciatic nerve regeneration. We studied the effects on this defect of treatment with the aldose reductase inhibitor, ponalrestat (25 mg/kg per day via an endogastric tube). The nerves of diabetic rats were crush-injured at 5 weeks of diabetes and regeneration evaluated 7 days later with the pinch-reflex test. Ponalrestat treatment was started at day 3 after streptozotocin injection and was continued for the whole experimental period, i.e. until 6 weeks of diabetes. The treatment prevented effectively the accumulation of sorbitol and fructose in the nerves of diabetic rats, but was without effect on the sciatic nerve regeneration (controls 21.8 ± 1.2 mm/7 days (mean ± SEM, n = 6), untreated diabetics 15.8 ± 1.8 (n = 7), ponalrestat-treated diabetics 16.2 ± 1.0 (n = 10)). The results indicate that there is no connection between increased sorbitol pathway flux and impaired regeneration in streptozotocin diabetic rats.
4.
5.
Simonsson, Stina, 1969, et al.
(författare)
Stem cell reprogramming: generation of patient-specific stem cells by somatic cell nuclear reprogramming.
2009
Ingår i: Drug Discovery Today: Technologies. ; xxx:x
Forskningsöversikt (refereegranskat) abstract
Human embryonic stem cells (hESCs) are a very attractive supply in medicine, in particular as a human model system in drug discovery and developmental biology, but could also be used in cell replacement therapy. We are learning about molecular signaling pathways from several animal models, some of which are directly applicable to human beings. However, several pathways are unique for human cells and therefore culture of human tissue is an important tool to decipher molecular events in the human system. Human embryonic stem cells have several advantages including their capacity to multiply indefinitely in tissue culture and their ability to differentiate into any cell type of the body. Today, technology exists for producing embryonic stem cells (ESCs) containing patientspecific genome. These cells can multiply in tissue culture and upon external signals be induced to differentiate into any cell type of interest. In this way, patient-specific dopamine producing nerve cells can be transplanted to patients suffering from Parkinson’s disease or patient-specific skin cells can be grafted in individuals suffering from melanoma cancer. Such cells could also provide a unique model system for patientspecific drug screening. This review describes historical breakthroughs underlying these advances and some of the technical obstacles to overcome.
6.
Tjernberg, L. O., et al.
(författare)
Transmissible amyloid
2016
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 280:2, s. 153-163
Forskningsöversikt (refereegranskat) abstract
There are around 30 human diseases associated with protein misfolding and amyloid formation, each one caused by a certain protein or peptide. Many of these diseases are lethal and together they pose an enormous burden to society. The prion protein has attracted particular interest as being shown to be the pathogenic agent in transmissible diseases such as kuru, Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Whether similar transmission could occur also in other amyloidoses such as Alzheimer's disease, Parkinson's disease and serum amyloid A amyloidosis is a matter of intense research and debate. Furthermore, it has been suggested that novel biomaterials such as artificial spider silk are potentially amyloidogenic. Here, we provide a brief introduction to amyloid, prions and other proteins involved in amyloid disease and review recent evidence for their potential transmission. We discuss the similarities and differences between amyloid and silk, as well as the potential hazards associated with protein-based biomaterials. Read more articles from the symposium: Amyloid - a multifaceted player in human health and disease.
7.
Hansson, Gunnar C., 1951
(författare)
Role of mucus layers in gut infection and inflammation.
2012
Ingår i: Current opinion in microbiology. - : Elsevier BV. - 1879-0364 .- 1369-5274. ; 15:1, s. 57-62
Forskningsöversikt (refereegranskat) abstract
The intestinal mucus is an efficient system for protecting the epithelium from bacteria by promoting their clearance and separating them from the epithelial cells, thereby inhibiting inflammation and infection. The function of the colon inner mucus layer is especially important as this explains how we can harbor the large number of bacteria in our gut. The major component of this mucus system is the MUC2 mucin which organizes the mucus by its enormously large net-like polymers. Pathogenic microorganisms, in turn, have developed mechanisms for circumventing this well-organized mucus protective system.
8.
Belizário, José E., et al.
(författare)
Skeletal muscle wasting and renewal : a pivotal role of myokine IL-6
2016
Ingår i: SpringerPlus. - : Springer Science and Business Media LLC. - 2193-1801. ; 5:1
Forskningsöversikt (refereegranskat) abstract
Adult skeletal tissue is composed of heterogeneous population of cells that constantly self-renew by means of a controlled process of activation and proliferation of tissue-resident stem cells named satellite cells. Many growth factors, cytokines and myokines produced by skeletal muscle cells play critical roles in local regulation of the inflammatory process and skeletal muscle regeneration during different pathological conditions. IL-6 is a pleiotropic cytokine released in large amount during infection, autoimmunity and cancer. Low levels of IL-6 can promote activation of satellite cells and myotube regeneration while chronically elevated production promote skeletal muscle wasting. These distinct effects may be explained by a crosstalk of the IL-6/IL-6 receptor and gp130 trans-signaling pathway that oppose to regenerative and anti-inflammatory of the classical IL-6 receptor signaling pathway. Here we discuss on potential therapeutic strategies using monoclonal antibodies to IL-6R for the treatment of skeletal muscle wasting and cachexia. We also highlight on the IL-6/JAK/STAT and FGF/p38αβ MAPK signaling pathways in satellite cell activation and the use of protein kinase inhibitors for tailoring and optimizing satellite cell proliferation during the skeletal muscle renewal. Future investigations on the roles of the IL-6 classical and trans-signaling pathways in both immune and non-immune cells in skeletal muscle tissue will provide new basis for therapeutic approaches to reverse atrophy and degeneration of skeletal muscles in cancer and inflammatory diseases.
9.
Carlsson, Robert, et al.
(författare)
Molecular Regulation of the Response of Brain Pericytes to Hypoxia
2023
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 24:6
Forskningsöversikt (refereegranskat) abstract
The brain needs sufficient oxygen in order to function normally. This is achieved by a large vascular capillary network ensuring that oxygen supply meets the changing demand of the brain tissue, especially in situations of hypoxia. Brain capillaries are formed by endothelial cells and perivascular pericytes, whereby pericytes in the brain have a particularly high 1:1 ratio to endothelial cells. Pericytes not only have a key location at the blood/brain interface, they also have multiple functions, for example, they maintain blood–brain barrier integrity, play an important role in angiogenesis and have large secretory abilities. This review is specifically focused on both the cellular and the molecular responses of brain pericytes to hypoxia. We discuss the immediate early molecular responses in pericytes, highlighting four transcription factors involved in regulating the majority of transcripts that change between hypoxic and normoxic pericytes and their potential functions. Whilst many hypoxic responses are controlled by hypoxia-inducible factors (HIF), we specifically focus on the role and functional implications of the regulator of G-protein signaling 5 (RGS5) in pericytes, a hypoxia-sensing protein that is regulated independently of HIF. Finally, we describe potential molecular targets of RGS5 in pericytes. These molecular events together contribute to the pericyte response to hypoxia, regulating survival, metabolism, inflammation and induction of angiogenesis.
10.
Danielsson, Frida, et al.
(författare)
Vimentin Diversity in Health and Disease
2018
Ingår i: Cells. - : MDPI. - 2073-4409. ; 7:10
Forskningsöversikt (refereegranskat) abstract
Vimentin is a protein that has been linked to a large variety of pathophysiological conditions, including cataracts, Crohn's disease, rheumatoid arthritis, HIV and cancer. Vimentin has also been shown to regulate a wide spectrum of basic cellular functions. In cells, vimentin assembles into a network of filaments that spans the cytoplasm. It can also be found in smaller, non-filamentous forms that can localise both within cells and within the extracellular microenvironment. The vimentin structure can be altered by subunit exchange, cleavage into different sizes, re-annealing, post-translational modifications and interacting proteins. Together with the observation that different domains of vimentin might have evolved under different selection pressures that defined distinct biological functions for different parts of the protein, the many diverse variants of vimentin might be the cause of its functional diversity. A number of review articles have focussed on the biology and medical aspects of intermediate filament proteins without particular commitment to vimentin, and other reviews have focussed on intermediate filaments in an in vitro context. In contrast, the present review focusses almost exclusively on vimentin, and covers both ex vivo and in vivo data from tissue culture and from living organisms, including a summary of the many phenotypes of vimentin knockout animals. Our aim is to provide a comprehensive overview of the current understanding of the many diverse aspects of vimentin, from biochemical, mechanical, cellular, systems biology and medical perspectives.
