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Benito-Cuesta I, Ordoñez-Gutierrez L, Wandosell F. Trehalose Reduces the Secreted Beta-Amyloid Levels in Primary Neurons Independently of Autophagy Induction. Metabolites. 2021;11(7)doi: 10.3390/metabo11070421.
Benito-Cuesta, I., Ordoñez-Gutierrez, L., & Wandosell, F. (2021). Trehalose Reduces the Secreted Beta-Amyloid Levels in Primary Neurons Independently of Autophagy Induction. Metabolites, 11(7), . https://doi.org/10.3390/metabo11070421
Benito-Cuesta, Irene, et al. "Trehalose Reduces the Secreted Beta-Amyloid Levels in Primary Neurons Independently of Autophagy Induction." Metabolites vol. 11,7 (2021). doi: https://doi.org/10.3390/metabo11070421
Benito-Cuesta I, Ordoñez-Gutierrez L, Wandosell F. Trehalose Reduces the Secreted Beta-Amyloid Levels in Primary Neurons Independently of Autophagy Induction. Metabolites. 2021 Jun 26;11(7). doi: 10.3390/metabo11070421. PMID: 34206776; PMCID: PMC8306653.
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Metabolites. 2021 Jun 26;11(7). doi: 10.3390/metabo11070421.

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

Metabolites

Irene Benito-Cuesta, Lara Ordoñez-Gutierrez, Francisco Wandosell

Affiliations

  1. Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, 28049 Madrid, Spain.
  2. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 28049 Madrid, Spain.

PMID: 34206776 PMCID: PMC8306653 DOI: 10.3390/metabo11070421

Abstract

The disaccharide trehalose was described as possessing relevant neuroprotective properties as an mTORC1-independent inducer of autophagy, with the ability to protect cellular membranes and denaturation, resulting from desiccation, and preventing the cellular accumulation of protein aggregates. These properties make trehalose an interesting therapeutic candidate against proteinopathies such as Alzheimer's disease (AD), which is characterized by deposits of aggregated amyloid-beta (Aβ) and hyperphosphorylated tau. In this study, we observed that trehalose was able to induce autophagy in neurons only in the short-term, whereas long-term treatment with trehalose provoked a relevant anti-amyloidogenic effect in neurons from an AD mouse model that was not mediated by autophagy. Trehalose treatment reduced secreted Aβ levels in a manner unrelated to its intracellular accumulation or its elimination through endocytosis or enzymatic degradation. Moreover, the levels of Aβ precursor protein (APP) and beta-secretase (BACE1) remained unaltered, as well as the proper acidic condition of the endo-lysosome system. Instead, our results support that the neuroprotective effect of trehalose was mediated by a reduced colocalization of APP and BACE1 in the cell, and, therefore, a lower amyloidogenic processing of APP. This observation illustrates that the determination of the mechanism, or mechanisms, that associate APP and BACE is a relevant therapeutic target to investigate.

Keywords: Alzheimer; SH-SY5Y; amyloid accumulation; autophagy; bafilomycin A1; cultured cerebellar granule neuron; trehalose

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