Biochemical Society transactions
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Biochem. Soc. Trans. · Jun 2015
ReviewControl of translation in the cold: implications for therapeutic hypothermia.
Controlled whole-body cooling has been used since the 1950s to protect the brain from injury where cerebral blood flow is reduced. Therapeutic hypothermia has been used successfully during heart surgery, following cardiac arrest and with varied success in other instances of reduced blood flow to the brain. However, why reduced temperature is beneficial is largely unknown. ⋯ Concurrently studies have demonstrated the importance of the regulation of protein synthesis, translation, to the cooling response, which is also emerging as a targetable process in neurodegeneration. Through these studies the potential importance of the rewarming process following cooling is also beginning to emerge. Altogether, these lines of research present new opportunities to manipulate cooling pathways for therapeutic gain.
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Biochem. Soc. Trans. · Apr 2014
ReviewInsulin, incretins and other growth factors as potential novel treatments for Alzheimer's and Parkinson's diseases.
Recently, it has been shown that in patients with AD (Alzheimer's disease) and, to some degree, in patients with PD (Parkinson's disease) insulin signalling is impaired. This finding has initiated a range of research projects that showed remarkable improvements using treatments that initially had been developed to treat diabetes. Pre-clinical studies showed good neuroprotective effects when applying insulin or long-lasting analogues of incretin peptides. ⋯ A pilot study in PD patients testing a GLP-1 receptor agonist that is currently on the market as a treatment for Type 2 diabetes also showed encouraging effects. Several other clinical trials are currently ongoing in AD patients. The present review summarizes the range of neuroprotective effects that these drugs have demonstrated and emphasizes the great promise that this approach has in providing novel treatments that have protective and even restorative properties that no current drug treatment can offer.
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The CRISPRs (clustered regularly interspaced short palindromic repeats) and their associated Cas (CRISPR-associated) proteins are a prokaryotic adaptive defence system against foreign nucleic acids. The CRISPR array comprises short repeats flanking short segments, called 'spacers', which are derived from foreign nucleic acids. ⋯ Adaptation allows the system to rapidly evolve against emerging threats. In the present article, we review the most recent studies on the adaptation process, and focus primarily on the subtype I-E CRISPR-Cas system of Escherichia coli.
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Biochem. Soc. Trans. · Aug 2012
ReviewDegradation of tau protein by autophagy and proteasomal pathways.
Tau aggregates are present in several neurodegenerative diseases and correlate with the severity of memory deficit in AD (Alzheimer's disease). However, the triggers of tau aggregation and tau-induced neurodegeneration are still elusive. ⋯ In the present paper, we focus on the regulation of the degradation of tau by the UPS and ALS and its relation to tau aggregation. We anticipate that stimulation of these two protein-degradation systems might be a potential therapeutic strategy for AD and other tauopathies.
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Biochem. Soc. Trans. · Apr 2010
ReviewThe anti-allodynic alpha(2)delta ligand pregabalin inhibits the trafficking of the calcium channel alpha(2)delta-1 subunit to presynaptic terminals in vivo.
Neuropathic pain is caused by lesion or dysfunction of the peripheral sensory nervous system. Up-regulation of the voltage-gated Ca(2+) channel subunit alpha(2)delta-1 in DRG (dorsal root ganglion) neurons and the spinal cord correlates with the onset of neuropathic pain symptoms such as allodynia in several animal models of neuropathic pain. The clinically important anti-allodynic drugs gabapentin and pregabalin are alpha(2)delta-1 ligands, but how these drugs alleviate neuropathic pain is poorly understood. In the present paper, we review recent advances in our understanding of their molecular mechanisms.