Trehalose accelerates the clearance of mutant huntingtin

HD Lighthouse Contributing Editor's Comment: Trehalose is a sugar that is approved for commercial use in the United States. Interest in trehalose as a potential treatment for Huntington's disease is based on research which shows that it

In this study, the researchers show that trehalose also stimulates autophagy which is a process which clears away the HD protein fragments from the cell by surrounding them and ‘consuming’ them. Enhanced clearance of the HD protein reduces its toxic effect.

Rapamycin also induces autophagy but it does so in a different manner than trehalose and the two of them together are more effective than either separately. See http://www.hdlighthouse.org/research/drugs-supps/updates/1068rapamycin.php

For those who are interested, trehalose can be purchased here: http://www.brooklynpremium.com/neurocoat.html

-- Marsha L. Miller, Ph.D.
Posted to the HDL: 12-26-2006

David C. Rubinsztein, Ph.D., Professor of Molecular Neurogenetics, University of Cambridge

Trehalose, a novel mTOR-independent autophagy enhancer,accelerates the clearance of mutant huntingtin and alpha-synuclein.

Sarkar S, Davies JE, Huang Z, Tunnecliffe A., and Rubinsztein D.

Trehalose, a disaccharide present in many non-mammalian species, protects cells against various environmental stresses. While some of its protective effects may be explained by its chemical chaperone properties, its actions are largely unknown. Here we report a novel function of trehalose as an mTOR independent autophagy activator. Trehalose-induced autophagy enhanced the clearance of autophagy substrates like mutant huntingtin and the A30P and A53T mutants of a-synuclein, associated with Huntington's disease (HD) and Parkinson's disease (PD), respectively. Furthermore, trehalose and mTOR inhibition by rapamycin together exert an additive effect on the clearance of these aggregate-prone proteins due to increased autophagic activity. By inducing autophagy, we showed that trehalose also protects cells against subsequent proapoptotic insults via the mitochondrial pathway. The dual protective properties of trehalose (as an inducer of autophagy and chemical chaperone) and the combinatorial strategy with rapamycin may be relevant to the treatment of HD and related diseases, where the mutant proteins are autophagy substrates.

Source: The Journal of Biological Chemistry 2006 Dec 20; [Epub ahead of print]