Mar 11, 2020

Neuronal Aquaporin 1 inhibits amyloidogenesis by suppressing the interaction between beta-secretase and amyloid precursor protein

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Jinsu ParkDong-Gyu Jo

Abstract

The accumulation of amyloid β (Aβ) is a characteristic event in the pathogenesis of Alzheimer's disease (AD). Aquaporin 1 (AQP1) is a membrane water channel protein belonging to the AQP family. AQP1 levels are elevated in the cerebral cortex during the early stages of AD, but the role of AQP1 in AD pathogenesis is unclear. We first determined the expression and distribution of AQP1 in brain tissue samples of AD patients and two AD mouse models (3xTg-AD and 5xFAD). AQP1 accumulation was observed in vulnerable neurons in the cerebral cortex of AD patients, and in neurons affected by the Aβ or tau pathology in the 3xTg-AD and 5xFAD mice. AQP1 levels increased in neurons as aging progressed in the AD mouse models. Stress stimuli increased AQP1 in primary cortical neurons. In response to cellular stress, AQP1 appeared to translocate to endocytic compartments of β- and γ-secretase activities. Ectopic expression of AQP1 in human neuroblastoma cells overexpressing amyloid precussir protein (APP) with the Swedish mutations reduced β-secretase (BACE1)-mediated cleavage of APP and reduced Aβ production without altering the non-amyloidogenic pathway. Conversely, knockdown of AQP1 enhanced BACE1 activity and Aβ production. Immunoprecipitati...Continue Reading

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Mentioned in this Paper

Ion Channel
Signal Pathways
Protein Expression
Cerebral Cortex
Gamma-Secretase
Neurons
Stress
Laboratory mice
Mouse Model
Amyloid beta-Peptides

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