The FEBS journal
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Because clinical trials of pharmacological neuroprotective strategies in stroke have been disappointing, attention has turned to the brain's own endogenous strategies for neuroprotection. Two endogenous mechanisms have been characterized so far, namely ischemic preconditioning and ischemic postconditioning. The neuroprotective concept of preconditioning is based on the observation that a brief, noninjurious episode of ischemia is able to protect the brain from a subsequent longer ischemic insult. ⋯ Many pathways have been proposed as plausible mechanisms to explain the neuroprotection offered by preconditioning and postconditioning. Unfortunately, so far, none of them has clearly identified the mechanism involved in preconditioning and postconditioning. The present article will review the main mechanisms reported to date to explain the neuroprotective effect of both ischemic preconditioning and postconditioning.
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The issue of how a newly synthesized polypeptide chain folds to form a protein with a unique three-dimensional structure, otherwise known as the 'protein-folding problem', remains a fundamental question in the life sciences. Over the last few decades, much information has been gathered about the mechanisms by which proteins fold. However, despite the vast topological diversity observed in biological structures, it was thought improbable, if not impossible, that a polypeptide chain could 'knot' itself to form a functional protein. ⋯ Their formation does not fit any current folding models or mechanisms, and therefore represents an important piece of the protein-folding puzzle. This article reviews the progress made towards discovering how nature codes for, and contends with, knots during protein folding, and examines the insights gained from both experimental and computational studies. Mechanisms to account for the formation of knotted structures that were previously thought unfeasible, and their implications for protein folding, are also discussed.