Induction of autophagy by a novel small molecule improves aβ pathology and ameliorates cognitive deficits.
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 str...
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Public Library of Science (PLoS)
2013
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oai:doaj.org-article:c07d0e99046f4a42acff63418245e0742021-11-18T07:43:04ZInduction of autophagy by a novel small molecule improves aβ pathology and ameliorates cognitive deficits.1932-620310.1371/journal.pone.0065367https://doaj.org/article/c07d0e99046f4a42acff63418245e0742013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23750258/?tool=EBIhttps://doaj.org/toc/1932-6203Growing 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.Cheng ChuXinjiang ZhangWei MaLi LiWei WangLu ShangPeng FuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e65367 (2013) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Cheng Chu Xinjiang Zhang Wei Ma Li Li Wei Wang Lu Shang Peng Fu Induction of autophagy by a novel small molecule improves aβ pathology and ameliorates cognitive deficits. |
| description |
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. |
| format |
article |
| author |
Cheng Chu Xinjiang Zhang Wei Ma Li Li Wei Wang Lu Shang Peng Fu |
| author_facet |
Cheng Chu Xinjiang Zhang Wei Ma Li Li Wei Wang Lu Shang Peng Fu |
| author_sort |
Cheng Chu |
| title |
Induction of autophagy by a novel small molecule improves aβ pathology and ameliorates cognitive deficits. |
| title_short |
Induction of autophagy by a novel small molecule improves aβ pathology and ameliorates cognitive deficits. |
| title_full |
Induction of autophagy by a novel small molecule improves aβ pathology and ameliorates cognitive deficits. |
| title_fullStr |
Induction of autophagy by a novel small molecule improves aβ pathology and ameliorates cognitive deficits. |
| title_full_unstemmed |
Induction of autophagy by a novel small molecule improves aβ pathology and ameliorates cognitive deficits. |
| title_sort |
induction of autophagy by a novel small molecule improves aβ pathology and ameliorates cognitive deficits. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/c07d0e99046f4a42acff63418245e074 |
| work_keys_str_mv |
AT chengchu inductionofautophagybyanovelsmallmoleculeimprovesabpathologyandamelioratescognitivedeficits AT xinjiangzhang inductionofautophagybyanovelsmallmoleculeimprovesabpathologyandamelioratescognitivedeficits AT weima inductionofautophagybyanovelsmallmoleculeimprovesabpathologyandamelioratescognitivedeficits AT lili inductionofautophagybyanovelsmallmoleculeimprovesabpathologyandamelioratescognitivedeficits AT weiwang inductionofautophagybyanovelsmallmoleculeimprovesabpathologyandamelioratescognitivedeficits AT lushang inductionofautophagybyanovelsmallmoleculeimprovesabpathologyandamelioratescognitivedeficits AT pengfu inductionofautophagybyanovelsmallmoleculeimprovesabpathologyandamelioratescognitivedeficits |
| _version_ |
1718423060237778944 |