RT Journal Article
T1 Trehalose Reduces the Secreted Beta-Amyloid Levels in Primary Neurons Independently of Autophagy Induction
A1 Benito-Cuesta, Irene
A1 Ordóñez Gutiérrez, Lara
A1 Wandosell, Francisco
AB 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.
PB MDPI
SN 2218-1989
YR 2021
FD 2021
LK https://hdl.handle.net/20.500.14352/113856
UL https://hdl.handle.net/20.500.14352/113856
LA eng
NO 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):421. doi: 10.3390/metabo11070421. PMID: 34206776; PMCID: PMC8306653.
NO Spanish Ministry of Science, Innovation and University
NO Comunidad de Madrid
NO Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
DS Docta Complutense
RD 8 abr 2025