Public Release:  A*STAR scientists discover protein's role in human memory and learning functions

Deficiency in SNX27 could explain the learning difficulties in Down's syndrome

Biomedical Sciences Institutes (BMSI)

1. Scientists at A*STAR's Institute of Molecular and Cell Biology (IMCB) have identified the precise role of the protein, SNX27, in the pathway leading to memory and learning impairment. The study broadens the understanding of the brain's memory function and could be used to explain defects in the cognitive development of those with Down's syndrome. The newly established knowledge could potentially facilitate exploration of strategies to improve memory and learning abilities in Down's syndrome.

2. Down's syndrome is a genetic condition characterized by the presence of an additional copy of chromosome 21. About one in eight hundred new-borns is diagnosed with Down's syndrome. It is a condition that leads to impairments in both cognitive ability and physical growth that range from mild to moderate developmental disabilities. Yet, there is still no treatment for it.

3. In an earlier study published in Nature Medicine, an international team of scientists discovered that the additional copy of chromosome 21 in Down's syndrome reduces the production of SNX27 in the brain and results in synaptic dysfunction. Synapse, a structure that permits nerve cells to pass chemical signals to each other, is known to have an important role in memory formation and its dysfunction could result in impairment. By re-introducing SNX27 into the brain, memory could be restored hence suggesting that SNX27 is an essential protein for memory and learning.

4. The protein's role in the pathway leading to memory impairment, however, remained unclear until scientists from IMCB utilised live-cell imaging techniques to elucidate the mechanism of memory impairment and illustrated how SNX27 attributes to synaptic dysfunction. The scientists observed that transmission of chemical signals between the nerve cells are facilitated by AMPA-receptors and the activity occurs on the brain cell surface. As SNX27 plays an important role in shuttling the AMPA-receptor to the brain cell surface, lower levels of SNX27 means fewer receptors are carried to the surface, which consequently interrupts the signal transmission and impairs memory. This discovery was reported in the 24 January, 2014 issue of the renowned scientific journal, Nature Communications.

5. The correlation established between SNX27 levels and memory could explain why individuals with Down's syndrome encounter memory and learning difficulties. Identifying the target and its role is a crucial first step to therapy - having known the role of SNX27 in memory impairment, future research on Down's syndrome could focus on developing strategies which can effectively re-introduce the protein into the brain to restore memory and learning abilities.

6. Dr Loo Li Shen was an A*STAR scholar who is now working with Executive Director of IMCB, Prof Wanjin Hong, and is also an adjunct Assistant Professor at LKC medical school of NTU. The lead author of the Nature Communications paper and co-author of the Nature Medicine paper said, "Memory and the ability to learn capture the essence of life. Our research goes beyond the lab to make a difference by finding ways to grant these fundamental capabilities to those diagnosed with Down's syndrome. Our ultimate goal is to create a positive impact on the lives of these valuable children."

7. Prof Hong added, "In IMCB, we conduct research that would contribute to our understanding of mankind. This is a good example where the study is directed at a human condition - the Down's syndrome. The knowledge established from the findings could potentially translate into treatments for Down's syndrome or even become applicable to other similar human conditions."

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Brain nerve cell studded with SNX27
(yellow-to-orange bulb-like structures)
(Image from Loo Li Shen, IMCB)

Notes for Editor:

The research findings described in this media release can be found in the 24 January, 2014 issue of Nature Communications Journal, under the title, "A role for sorting nexin 27 in AMPA receptor trafficking" by Li Shen Loo1,2, Ning Tang3, Muthafar Al-Haddawi1, Gavin Stewart Dawe3 & Wanjin Hong1,4,12 and the 24 March, 2013 issue of Nature Medicine Journal, under the title, "Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down's syndrome" by Xin Wang5,6, Yingjun Zhao5,7, Xiaofei Zhang5, Hedieh Badie8, Ying Zhou6, Yangling Mu9, Li Shen Loo1,2, Lei Cai1, Robert C Thompson5, Bo Yang5, Yaomin Chen5, Peter F Johnson10, Chengbiao Wu11, Guojun Bu7, William C Mobley11, Dongxian Zhang5, Fred H Gage9, Barbara Ranscht8, Yun-wu Zhang5,7, Stuart A Lipton5,11, Wanjin Hong1,4,12 & Huaxi Xu5,7

1Institute of Molecular and Cell Biology, Singapore 138673, Singapore.
2Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
637553, Singapore.
3Department of Pharmacology, Neurobiology and Ageing Programme, Singapore Institute for Neurotechnology, National University of Singapore, Singapore 117597, Singapore.
4Department of Biochemistry, National University of Singapore, Singapore 117597, Singapore.
5Center for Neuroscience, Aging and Stem Cell Research, Sanford-Burnham Medical Research Institute, La Jolla, California, USA.
6Graduate School of Biomedical Sciences, Sanford-Burnham Medical Research Institute, La Jolla, California, USA.
7Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Medical College, Xiamen University, Xiamen, China.
8Tumor Microenvironment Program, Sanford-Burnham Medical Research Institute, La Jolla, California, USA.
9Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California, USA.
10Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland, USA.
11Department of Neurosciences, University of California San Diego, La Jolla, California, USA.
12Institute for Biomedical Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.

Correspondence for the Nature Communications publication should be addressed to L.S.L. (email: lsloo@imcb.a-star.edu.sg) Correspondence for the Nature Medicine publication should be addressed to H.X. (xuh@sanfordburnham.org or hxxu@xmu.edu.cn)

Full text of the Nature Communication article can be accessed from http://www.nature.com/ncomms/2014/140124/ncomms4176/full/ncomms4176.html Full text of the Nature Medicine article can be accessed from http://www.nature.com/nm/journal/v19/n4/full/nm.3117.html

AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH (A*STAR)

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About Institute of Molecular and Cell Biology (IMCB)

The Institute of Molecular and Cell Biology (IMCB) was established in 1987 at the National University of Singapore (NUS) before becoming an autonomous research institute (RI) of A*STAR and moving to Biopolis in 2004. IMCB strives to maintain the scientific excellence of PI-driven research and at the same time aims to promote collaborative team-based projects of medical and industrial relevance. Funded primarily by the Biomedical Research Council (BMRC) of A*STAR, IMCB's research activities focus on four major fields: Animal Models of Development and Disease, Cancer Genetics and Therapeutics, Cell Biology in Health and Disease, and Structural Biology and Drug Discovery. For more information about IMCB, please visit http://www.imcb.a-star.edu.sg.

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy.

In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore's manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry.

A*STAR oversees 18 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis, as well as their vicinity. These two R&D hubs house a bustling and diverse community of local and international research scientists and engineers from A*STAR's research entities as well as a growing number of corporate laboratories.

For more information about A*STAR, please visit http://www.a-star.edu.sg.

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