Trehalose against Alzheimer's Disease: Insights into a Potential Therapy

Abstract

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.

Fractions of traditionally brewed rice beverage ameliorate anxiety and improve spatial memory in mice

“…Cinnamic acid and Threonic acid have also shown memory enhancing activities [20]. Further, sugars like Allose and Trehalose exert neuroprotective activities [21,22]. From the NGS data, 574030 quality reads showed a significant homology with predicted rRNA sequences in the Greengene database.…”

The Role of HSPB8, a Component of the Chaperone-Assisted Selective Autophagy Machinery, in Cancer

“…An example is the disaccharide trehalose that activates autophagy via the lysosomalmediated TFEB pathway [131,132]. By activating autophagy, trehalose assists the removal of several toxic misfolded proteins [131,[133][134][135], and, not surprisingly, trehalose has been proven as a therapeutic approach in in vitro and in vivo cancer models [136][137][138]. Of note, still related to PQC modulation, HSPB8 and BAG3 expression has been found to respond to some proteotoxic stress via the activation of the NF-κB transcription factor [22,73].…”

Trehalose Reduces the Secreted Beta-Amyloid Levels in Primary Neurons Independently of Autophagy Induction

“…Trehalose has shown relevant neuroprotective functions as a potent mTORC1-independent autophagic inductor [ 2 , 3 , 4 , 5 ]. However, there is no general consensus regarding the mechanism of the induction of autophagy [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Moreover, this disaccharide is considered to protect cellular membranes, preventing protein denaturation by direct unions, thus protecting the cell against environmental stresses [ 1 , 13 ].…”

“…Moreover, this disaccharide is considered to protect cellular membranes, preventing protein denaturation by direct unions, thus protecting the cell against environmental stresses [ 1 , 13 ]. These properties make trehalose an interesting therapeutic approach against neurodegenerative proteinopathies such as Alzheimer’s disease (AD) [ 10 ]. As post-mitotic cells, neurons are especially vulnerable since they cannot dilute harmful protein aggregates or dysfunctional organelles through cellular division [ 14 ].…”

“…The main beta-secretase (BACE1) processes APP mostly after its internalization in late endosomes and lysosomes, since BACE1 needs an acidic pH for optimal endoproteolytic activity [ 19 , 20 ]. An accumulation of Aβ-containing autophagic vesicles, whose maturation and degradation remain impaired, was described in AD [ 10 ]. Increasing evidence supports the promotion of autophagy as a therapeutic strategy for the amelioration of such AD pathology [ 21 , 22 ], and trehalose has been proposed as a therapeutic mTOR-independent autophagy inducer in several neurodegenerative diseases [ 2 , 5 , 10 ].…”