Trehalose is a natural disaccharide with a remarkable ability to stabilize biomolecules. In recent years, trehalose has received growing attention as a neuroprotective molecule and has been tested in experimental models for different neurodegenerative diseases. Although the underlying neuroprotective mechanism of trehalose's action is unclear, one of the most important hypotheses is autophagy induction. The chaperone‐like activity of trehalose and the ability to modulate inflammatory responses has also been reported. There is compelling evidence that the dysfunction (...) of autophagy and aggregation of misfolded proteins contribute to the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. Therefore, given the linking between trehalose and autophagy induction, it appears to be a promising therapy for AD. Herein, the published studies concerning the use of trehalose as a potential therapy for AD are summarized, providing a rationale for applying trehalose to reduce Alzheimer's pathology. (shrink)

Over 300 years ago the father of microscopy, Antonie van Leeuwenhoek, observed dried rotifers “coming back to life” upon rehydration. Since then, scientists have been fascinated by the enduring mystery of how certain organisms survive losing essentially drying out completely. Historically sugars, such as the disaccharide trehalose, have been viewed as major functional mediators of desiccation tolerance. However, some desiccation tolerant organisms do not produce this sugar, hinting that additional mediators, and potentially novel mechanisms exist. It has become apparent (...) that a common theme among such organisms is the production and use of intrinsically disordered proteins to mediate survival in this dry state. However, the basic biology of these proteins – which unlike globular proteins lack persistent three-dimensional structure – is poorly understood, as are the functional mechanisms utilized by these enigmatic proteins that allow them to mediate desiccation tolerance. We purpose that probing the biochemical and biophysical nature of stress-related IDPs will provide mechanistic insights into these fascinating proteins. Remarkably, organisms from every kingdom of life can survive losing nearly all their intracellular water. A hallmark of desiccation tolerance is the use of intrinsically disordered proteins, but how IDPs contribute to tolerance is poorly understood. Here, we discuss possible mechanisms and avenues for studying these enigmatic proteins. (shrink)