23 February, 2013

Amyloid and Memory

"Whats the last thing that goes through a bug's mind as it hits the windshield of your car?"

The answer to this old joke ("it's a**hole") may turn out only to be true if said bug has defective Orb2, a member of a family of RNA-binding proteins called Cytoplasmic Polyadenylation Element-Binding Proteins (CPEB). If Orb2 is doing its job, the bug might instead have been reflecting on the one that got away at the moment of impact. 

As discussed in an interesting but rather technical article by Mujumdar A, et al., in drosophila (fruit flies) normal Orb2 forms degradation-resistant amyloid-like oligomers at neuronal synapses (in other words, functional amyloid in the connection points between brain nerve cells). These oligomers are essential to the persistence of long-term memory, which in this paper was determined by measuring "courtship suppression memory."  It goes something like this: a male fruit fly, after repeatedly being told to "buzz-off" by an uninterested female fruit fly, eventually learns to stop pestering her and other uninterested females. Normally, this newly-acquired behavior persists for days before waning. Although its tempting to discuss how eerily similar this sounds to a couple of desperate years in middle school, lets focus instead on what happens in fruit flies with mutant Orb2: within 24 hrs, they are back at it, pestering uninterested female fruit flies. A failure of long-term memory. 

Although CPEB is found in mammalian neurons too, and seems to play a role in memory formation, it isn't clear whether this is mediated by functional amyloid formation. As reviewed by J. Richter, stimulation of CPEB-containing nerve cells results in increases in specific neuronal proteins involved in memory persistence. Thus, it appears CPEB's function as a promotor of protein translation, rather than any amyloidogenic properties, may be the basis of its role in mammalian memory. Jury apparently still out, though. 

In the near future, I'll discuss another situation in which amyloid (amyloid-beta) plays a role in memory - in this case, the LOSS of memory - in people with Alzheimer's Dementia.    

No comments:

Post a Comment