Galectin-3 facilitates amyloid-beta oligomerization
Zheng, Kuang Min
Lee, Eminy H.Y.
Chao, Chih Chang
Zheng, Kuang Min
APP/PS1 transgenic mice
|上傳時間: ||2017-09-13 14:49:49 (UTC+8)|
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder which is characterized by progressive loss of memory and other cognitive functions. The two pathological hallmarks of AD are extracellular amyloid plaque and flame-shaped neurofibrillary tangles of the tau protein. Aβ is a 4-kDa protein that is resulted from sequential cleavage of the amyloid precursor protein by beta-secretase and gamma-secretase. Once Aβ is produced, it will aggregate to form oligomers and high molecular weight (HMW) oligomers will further assemble to form large insoluble fibrils and plaque. Galectin-3 (Gal-3) is a member of the β-galactoside-binding galectin protein family. Gal-3 is known to regulate various cellular functions, such as inflammation, tumor progression and cell-cell adhesion. In cancer cell, Gal-3 enhances homotypic aggregation, but its role in the brain is much less known. In the present study, we examined the role and mechanism of Gal-3 in Aβ aggregation in the brain by adopting the APP/PS1 mice as an animal model of AD. Results revealed that overexpression of Gal-3 enhanced Aβ oligomerization, whereas Aβ injection into hippocampus of Gal-3 KO mice reduced Aβ oligomerization. Aβ injection also increased Gal-3 expression in the hippocampus. Gal-3 expression is also increased in APP/PS1 mice and this effect is more significant along with ageing. Meanwhile, the expression of protein inhibitor of activated STAT1 (PIAS1) that suppresses inflammation and immune response was decreased with ageing in APP/PS1 mice. We further found that the expression level of neprilysin, an enzyme that degrades Aβ, was increased for approximately two-folds in Gal-3 KO mice compared with WT mice. These results suggest that Gal-3 plays an important role in Aβ aggregation and possibly in the pathology of AD.
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