[HTML][HTML] Induction of autophagy by a novel small molecule improves aβ pathology and ameliorates cognitive deficits

C Chu, X Zhang, W Ma, L Li, W Wang, L Shang, P Fu - PLoS One, 2013 - journals.plos.org
C Chu, X Zhang, W Ma, L Li, W Wang, L Shang, P Fu
PLoS One, 2013journals.plos.org
Growing evidence has demonstrated a neuroprotective role of autophagy in Alzheimer's
disease (AD). Thus, autophagy has been regarded as a potential therapeutic target,
attracting increasing interest in pharmaceutical autophagy modulation by small molecules.
We designed a two-cycle screening strategy on the basis of imaging high-throughout
screening (HTS) and cellular toxicity assay, and have identified a novel autophagy inducer
known as GTM-1. We further showed that GTM-1 exhibits dual activities, such as autophagy …
Growing evidence has demonstrated a neuroprotective role of autophagy in Alzheimer’s disease (AD). Thus, autophagy has been regarded as a potential therapeutic target, attracting increasing interest in pharmaceutical autophagy modulation by small molecules. We designed a two-cycle screening strategy on the basis of imaging high-throughout screening (HTS) and cellular toxicity assay, and have identified a novel autophagy inducer known as GTM-1. We further showed that GTM-1 exhibits dual activities, such as autophagy induction and antagonism against Aβ-oligomer toxicity. GTM-1 modulates autophagy in an Akt-independent and mTOR-independent manner. In addition, we demonstrated that GTM-1 enhances autophagy clearance and reverses the downregulation of autophagy flux by thapsigargin and asparagine. Furthermore, administration of GTM-1 attenuated Aβ pathology and ameliorated cognitive deficits in AD mice.
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