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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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« How Goes the War? | Main | Welcome to the Author's Brain. The "Fasten Seatbelts" Sign Is Illuminated »

August 29, 2013

A New Pathway For Memory

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Posted by Derek

As someone who will not be seeing the age of 50 again, I find a good deal of hope in a study out this week from Eric Kandel and co-workers at Columbia. In Science Translational Medicine, they report results from a gene expression study in human brain samples. Looking at the dentate gyrus region of the hippocampus, long known to be crucial in memory formation and retrieval, they found several proteins to have differential expression in younger tissue samples versus older ones. Both sets were from otherwise healthy individuals - no Alzheimer's, for example.

RbAp48 (also known as RBBP4 and NURF55), a protein involved in histone deacetylation and chromatin remodeling, stood out in particular. It was markedly decreased in the samples from older patients, and the same pattern was seen for the homologous mouse protein. Going into mice as a model system, the paper shows that knocking down the protein in younger mice causes them to show memory problems similar to elderly ones (object recognition tests and the good old Morris water maze), while overexpressing it in the older animals brings their performance back to the younger levels. Overall, it's a pretty convincing piece of work.

It should set off a lot of study of the pathways the protein's involved in. My hope is that there's a small-molecule opportunity in there, but it's too early to say. Since it's involved with histone coding, it could well be that this protein has downstream effects on the expression of others that turn out to be crucial players (but whose absolute expression levels weren't changed enough to be picked up in the primary study). Trying to find out what RbAp48 is doing will keep everyone busy, as will the question of how (and/or why) it declines with age. Right now, I think the whole area is wide open.

It is good to hear, though, that age-related memory problems may not be inevitable, and may well be reversible. My own memory seems to be doing well - everyone who knows me well seems convinced that my brain is stuffed full of junk, which detritus gets dragged out into the sunlight with alarming frequency and speed. But, like anyone else, I do get stuck on odd bits of knowledge that I think I should be able to call up quickly, but can't. I wonder if I'm as quick as I was when I was on Jeopardy almost twenty years ago, for example?

(If you don't have access to the journal, here's the news writeup from Science, and here's Sharon Begley at Bloomberg).

Comments (7) + TrackBacks (0) | Category: Aging and Lifespan | The Central Nervous System


COMMENTS

1. Henry's cat on August 29, 2013 10:49 AM writes...

Blah blah blah...The only question on everyone's lips is how well you did on Jeopardy...

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2. Anonymous on August 29, 2013 11:02 AM writes...

...assuming he can remember! :-)

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3. In Vivo Veritas on August 29, 2013 11:46 AM writes...

Derek came in a strong 2nd....... I hear that the guy who won was an MBA & 6-Sigma blackbelt, working at Boston Consulting!

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4. daen on August 29, 2013 1:25 PM writes...

I forgot what 'homeopathy' was called in the middle of a conversation the other night. I ended up describing it: "You know, vast dilutions to the total exclusion of bioactive ingredients; cultish adherents; that kind of thing!" (OK, there was whiskey involved).

Sadly, I can now remember what it's called again.

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5. smurf on August 29, 2013 1:40 PM writes...

Sharon Begley at Reuters, not Bloomberg, correct?

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6. SP on August 29, 2013 1:50 PM writes...

HDAC2 inhibitors (quite druggable) are known to have the same effect, maybe RBBP4 is in an acetylation complex with a corresponding HAT.

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7. Klimt Limped on August 29, 2013 4:33 PM writes...

For those of us dreading the influence of senescence, the other encouraging aspect of this research pertains to Kandel himself. At ~83 years of age, no spring chicken. The fact that he and his research group are contributing such original findings is hopeful and inspiring.

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