Alzheimer’s is a disease that seems to become more prevalent in our lives as the people around us age. A team of scientists from around the world, led by researchers from MIT's Picower Institute for Learning and Memory have identified a gene that has the ability to regain long-term memory and learning function in mice with Alzheimer’s symptoms. The particular gene and subsequent enzyme in the spotlight is histone deacetylase 2 (HDAC2) that regulates a group of genes responsible for the brains plasticity (brains ability to adapt and modify itself in response to experience and memory formation).
What the researchers have done is introduce HDAC inhibitors that target and stop the HDAC2 from tightly compacting the histones with DNA coiled around them. In doing so it allows more acetylation to occur resulting in a looser structured chromatin that is more accessible to transcription proteins (Campbell, Reece & Myers 2006). With the genes able to be transcribed more easily there becomes an abundance of genes responsible for brain plasticity available to act.
Transgenic mice underwent artificial brain atrophy associated with Alzheimer’s and displayed lack of memory and learning function. Introduction of HDAC inhibitors allowed the mice to regain previously learnt memories as well as assist in the formation of new learning abilities. The researchers also created some mice that had the HDAC2 genetically removed and found that the mice had enhanced memory function. This raises the theory that promoters of healthy memory functionality may just be inaccessible, locked away in a deacetylased state.
There is no doubt that removal of this particular gene raises interesting questions as to why the body would have this function if removal of it will increase memory function. When cells divide the DNA wraps around relative histones and compact to allow efficient separation (Campbell, Reece & Myers 2006). So will removal of HDAC2 lead to other possible complications in cell proliferation? Hopefully with further research continuing in this field, the future will look a little more memorable to sufferers of Alzheimer’s.
References:
Campbell, NA, Reece, JB & Meyers, N 2006, Biology, Seventh edn, Pearson Education Australia, Frenchs Forest
Guan, J-S, Haggarty, SJ, Giacometti, E, Dannenberg, J-H, Joseph, N, Goa, J, Nieland, TJF, Zhou, Y, Wang, X, Mazitschek, R, Bradner, JE, DePinho, RA, Jaenisch, R & Tsa, L-H 2009, 'HDAC2 Negatively Regulates Memory Formation and Synaptic Plactisity', Nature, vol. 459, no. 7243, pp. 55-60.
Source:
http://www.sciencedaily.com/releases/2009/05/090506144309.htm
Image:
http://sgc.utoronto.ca/SGC-WebPages/StructureDescription/img/2NVR_400x400.png
Crystal structure of a Histone Deacetylase.What the researchers have done is introduce HDAC inhibitors that target and stop the HDAC2 from tightly compacting the histones with DNA coiled around them. In doing so it allows more acetylation to occur resulting in a looser structured chromatin that is more accessible to transcription proteins (Campbell, Reece & Myers 2006). With the genes able to be transcribed more easily there becomes an abundance of genes responsible for brain plasticity available to act.
Transgenic mice underwent artificial brain atrophy associated with Alzheimer’s and displayed lack of memory and learning function. Introduction of HDAC inhibitors allowed the mice to regain previously learnt memories as well as assist in the formation of new learning abilities. The researchers also created some mice that had the HDAC2 genetically removed and found that the mice had enhanced memory function. This raises the theory that promoters of healthy memory functionality may just be inaccessible, locked away in a deacetylased state.
There is no doubt that removal of this particular gene raises interesting questions as to why the body would have this function if removal of it will increase memory function. When cells divide the DNA wraps around relative histones and compact to allow efficient separation (Campbell, Reece & Myers 2006). So will removal of HDAC2 lead to other possible complications in cell proliferation? Hopefully with further research continuing in this field, the future will look a little more memorable to sufferers of Alzheimer’s.
References:
Campbell, NA, Reece, JB & Meyers, N 2006, Biology, Seventh edn, Pearson Education Australia, Frenchs Forest
Guan, J-S, Haggarty, SJ, Giacometti, E, Dannenberg, J-H, Joseph, N, Goa, J, Nieland, TJF, Zhou, Y, Wang, X, Mazitschek, R, Bradner, JE, DePinho, RA, Jaenisch, R & Tsa, L-H 2009, 'HDAC2 Negatively Regulates Memory Formation and Synaptic Plactisity', Nature, vol. 459, no. 7243, pp. 55-60.
Source:
http://www.sciencedaily.com/releases/2009/05/090506144309.htm
Image:
http://sgc.utoronto.ca/SGC-WebPages/StructureDescription/img/2NVR_400x400.png
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