While ATP may help to solubilize proteins, I don't find it surprising the cells under question have very high ATP concentrations. I take issue with this statement:<p>> In addition to being an energy source for biological reactions, for which micromolar concentrations are sufficient, we propose that millimolar concentrations of ATP may act to keep proteins soluble. This may in part explain why ATP is maintained in such high concentrations in cells.<p>Sure it's important for neurons to prevent amyloid-beta from aggregating, but we can explain why neurons have a super high (mM) ATP concentration for two other good reasons:<p>1. Unlike other cells, neurons conduct electrical signals. Every time a neuron fires it opens channels that allow sodium and potassium to flow through the membrane. Then, it needs to get those ions back across the membrane so the neuron can keep functioning. To do this neurons make prodigious use of Na/K-ATPase pumps, that exchange intracellular Na for extracellular K, against an electrochemical gradient. This is active transport that requires tons of ATP. In a typical animal cell active transport is a relatively small (~1/10th) portion of cellular energy expenditure compared to neurons (~7/10th).<p>2. ATP is used in actin filament polymerization. Each molecule of filamentous actin is coupled to an ATP molecule, and actin is found in neurons at mM concentrations. Actin is a major structural protein in cells, and plays a particularly important role in neurons. Actin helps create filopodial protrusions; if you compare a neuron to another type of cell you can immediately tell it's a protrusion machine. Even these protrusions (axons and dendrites) have protrusions (neurites and dendritic spines) that are constantly reorganizing to allow for structural plasticity among the brain's neural network connections. One of my dissertation projects was to simulate actin activity in neurons; for anyone's interested, here are some pretty neat visuals of this...<p>Actin polymerization to create a dendritic spine:
<a href="https://youtu.be/JH-hGjzhEFQ" rel="nofollow">https://youtu.be/JH-hGjzhEFQ</a><p>Small segment of a dendrite with surface receptor diffusion:
<a href="https://www.youtube.com/embed/6ZNnBGgea0Y" rel="nofollow">https://www.youtube.com/embed/6ZNnBGgea0Y</a><p>Creating dendritic meshes in python:
<a href="https://youtu.be/tDKUU0SqbSA" rel="nofollow">https://youtu.be/tDKUU0SqbSA</a>
For broader context, this might be used to help explain the well known link between the age-related decline in mitochondrial function (and consequence lowered production rate of ATP) and the age-related development of aggregates such as amyloids and tau. Aggregates are age-related, but one needs explanations as to why that is the case. Other proximate causes include declining cellular garbage collection mechanisms, aggregation of other proteins (protein A spurs aggregation of protein B), failure of mechanical clearance via peristaltic channels, and so forth. It's never just one thing.<p>Like many lines of research manage to achieve, this finding adds a little more emphasis to the need to restore mitochondrial function in the old. Clearing damaged mitochondria, delivering replacement mitochondria to cells, allotopic expression of mitochondrial genes, and so forth.
Sounds kind of like a surfactant (<a href="https://en.wikipedia.org/wiki/Surfactant" rel="nofollow">https://en.wikipedia.org/wiki/Surfactant</a>)