The international journal of biochemistry & cell biology
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Int. J. Biochem. Cell Biol. · Jun 2020
ReviewThe pivotal role of ubiquitin-activating enzyme E1 (UBA1) in neuronal health and neurodegeneration.
Ubiquitin-activating enzyme E1, UBA1, functions at the apex of the enzymatic ubiquitylation cascade, catalysing ubiquitin activation. UBA1 is thus of fundamental importance to the modulation of ubiquitin homeostasis and to all downstream ubiquitylation-dependent cellular processes, including proteolysis through the ubiquitin-proteasome system and selective autophagy. ⋯ Moreover, ubiquitylation-independent functions of UBA1 of importance to neuronal functioning have been proposed. Here, we summarise findings supporting the significant role of UBA1 in regulating neuronal functioning, and discuss the detrimental consequences of UBA1 impairment that contribute to neuronal dysfunction and degeneration.
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Int. J. Biochem. Cell Biol. · Sep 2019
ReviewVirtual Reality interventions for acute and chronic pain management.
Virtual Reality (VR) is now consumer ready and nearing ubiquity. In terms of clinical applications, several studies suggest that VR can be effective as a complementary adjunct or alternative non-pharmacologic analgesic in a range of pain-inducing procedures and in management of chronic pain. ⋯ However, further research is needed to establish its long-term benefits if VR is to be adopted into mainstream protocols for analgesia management. This research requires a range of study designs with collection of patient self-report and clinical data together to develop bespoke interventions for different cohorts.
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Int. J. Biochem. Cell Biol. · May 2019
ReviewAntisense oligonucleotide therapies for Amyotrophic Lateral Sclerosis: Existing and emerging targets.
Amyotrophic lateral sclerosis (ALS) is a disease with highly heterogenous causes, most of which remain unknown, a multitude of possible disease mechanisms, and no therapy currently available that can halt disease progression. However, recent advances in antisense oligonucleotides have made them a viable option for targeted therapeutics for patients. ⋯ Furthermore, biological pathways involved in the pathogenesis of disease also offer tantalizing targets for intervention using antisense oligonucleotides. Here we detail existing and potential targets for antisense oligonucleotides in ALS and briefly examine the requirements for these drugs to reach and be effective in clinic.
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Int. J. Biochem. Cell Biol. · Feb 2018
ReviewThe good and bad faces of the CXCR4 chemokine receptor.
Chemokines are chemotactic cytokines that promote cell migration and activation under homeostatic and inflammatory conditions. Chemokines bind to seven transmembrane-spanning receptors that are coupled to heterotrimeric guanine nucleotide-binding (G) proteins, which are the responsible for intracellularly transmitting the activating signals for cell migration. Hematopoiesis, vascular development, lymphoid organ morphogenesis, cardiogenesis and neural differentiation are amongst the processes involving chemokine function. ⋯ The CXCL12 chemokine (also known as stromal-cell derived factor-1α, SDF-1α) plays key roles in hematopoiesis and lymphoid tissue architecture, in cardiogenesis, vascular formation and neurogenesis, as well as in the trafficking of solid and hematological cancer cell types. CXCL12 binds to the CXCR4 receptor, a multi-facetted molecule which tightly mirrors CXCL12 functions in homeostasis and disease. This review addresses the important roles of the CXCR4-CXCL12 axis in homeostasis, specially focusing in hematopoiesis, as well as it provides a picture of CXCR4 as mediator of cancer cell spreading, and a view of the available CXCR4 antagonists in different cancer types.
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Int. J. Biochem. Cell Biol. · Oct 2014
ReviewRelationships between cobalamin, epidermal growth factor, and normal prions in the myelin maintenance of central nervous system.
Cobalamin (Cbl), epidermal growth factor (EGF), and prions (PrPs) are key molecules for myelin maintenance in the central and peripheral nervous systems. Cbl and EGF increase normal prion (PrP(C)) synthesis and PrP(C) levels in rat spinal cord (SC) and elsewhere. Cbl deficiency increases PrP(C) levels in rat SC and cerebrospinal fluid (CSF), and decreases PrP(C)-mRNA levels in rat SC. ⋯ In rat frontal cortex (which is marginally affected by Cbl deficiency in histological terms), Cbl deficiency decreases PrP(C) levels and the increase induced by Cbl replacement leads to their normalization. Increased nerve PrP(C) levels are detected in the myelin lesions of the peripheral neuropathy of Cbl-D rats, and CSF PrP(C) levels are also increased in Cbl-D patients (but not in patients with Cbl-unrelated neurological diseases). Various common steps in the downstream signaling pathway of Cbl, EGF, and PrP(C) underlines the close relationship between the three molecules in keeping myelin normal.