Trehalose
A Sweet Solution
Trehalose, also known as mycose or tremalose, is a natural alpha-linked disaccharide formed by an α,α-1,1-glucoside bond between two α-glucose units. In addition to its mild sweetness and the fact that trehalose is chemically stable owing to the fact that it is a non-reducing sugar, it is also stable in acidic and high temperature conditions. Trehalose has been used in several biopharmaceutical monoclonal antibody formulations such as trastuzumab and bevacizumab.
It also shows promise in Alzheimer's research. A key event in Alzheimer's disease (AD) pathogenesis is the conversion of the peptide beta-amyloid (Abeta) from its soluble monomeric form into various aggregated morphologies in the brain. Preventing aggregation of Abeta is being actively pursued as a primary therapeutic strategy for treating AD. Trehalose, a simple disaccharide, has been shown to be effective in preventing the deactivation of numerous proteins and in protecting cells against stress.
Because of its unique chemical properties, trehalose has been the focus of study in several neurodegenerative diseases that are associated with the misfolding of disease-specific proteins. These conditions include Alzheimer's disease (AD), Huntington's disease (HD), and oculopharyngeal muscular dystrophy (OPMD). In each disease, specific misfolded aggregate-prone proteins are resistant to the normal cellular processes of protein turnover and accumulate in insoluble inclusions in regions specific to each disease. While insoluble aggregates correlate with disease progression, there is increasing evidence that the initiating and most toxic events are caused by soluble protein oligimers or microaggregates. Trehalose is thought to work by interfering with the production, and enhancing the destruction of aggregated proteins.
Trehalose is implicated in anhydrobiosis, the ability of plants and animals to withstand prolonged periods of desiccation.
Brine shrimp eggs, can remain dehydrated for years in a state of suspended animation due to their trehalose content. The resurrection plant and water bears (tardigrades) can also withstand long periods of dehydration followed by regeneration when water becomes available. When water dissipates from the shell of macromolecules (such as proteins and cell membranes) during severe dehydration, trehalose can act as a water substitute on the surface of the dried protein. Thus, the native folding and biological activity of proteins are maintained, and denaturation and aggregation are prevented.
The sugar is thought to form a gel phase as cells dehydrate, which prevents disruption of internal cell organelles by effectively splinting them in position. Rehydration then allows normal cellular activity to be resumed without the major, generally lethal damage, which would normally follow a dehydration/reyhdration cycle.
Ref: Liu R, Barkhordarian H, Emadi S, Park CB, Sierks MR; Neurobiol Dis. 2005 Oct; 20(1):74-81. Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42. http://www.ncbi.nlm.nih.gov/pubmed/16137568
