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

Sovan Sarkar, Janet E Davies, Zebo Huang, Alan Tunnacliffe, David C Rubinsztein

Research output: Contribution to journalArticlepeer-review

787 Citations (Scopus)


Trehalose, a disaccharide present in many non-mammalian species, protects cells against various environmental stresses. Whereas some of the 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 alpha-synuclein, associated with Huntington disease (HD) and Parkinson disease (PD), respectively. Furthermore, trehalose and mTOR inhibition by rapamycin together exerted an additive effect on the clearance of these aggregate-prone proteins because of increased autophagic activity. By inducing autophagy, we showed that trehalose also protects cells against subsequent pro-apoptotic 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.

Original languageEnglish
Pages (from-to)5641-52
Number of pages12
JournalJournal of Biological Chemistry
Issue number8
Publication statusPublished - 23 Feb 2007


  • Animals
  • Antibiotics, Antineoplastic
  • Autophagy
  • COS Cells
  • Cercopithecus aethiops
  • HeLa Cells
  • Humans
  • Huntington Disease
  • Mice
  • Molecular Chaperones
  • Mutation
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Parkinson Disease
  • Protein Kinases
  • Sirolimus
  • TOR Serine-Threonine Kinases
  • Trehalose
  • alpha-Synuclein


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