TwistedHelix wrote:... the discovery of a brand new pathway involving Rho, which can lead to cell death
Rho’s play a key role in regulating the actin cytoskeleton of the neuron that means – structural integrity and movements, mostly of dendrites/axons; presence of Rho is crucial for brain development. Rho’s are responsible not only for changes in axons configuration, they promote glial cells activation and their re-arrangement around the axon.
For any kind of movement the presence of calcium is mutual (like a gas for the car engine), no calcium - no movement. In mature cells Rho’s behave like a ‘gardener’ carefully pruning unused (or became unused) dendritic/axonal branches, maintain the current structure and promote carefully wrapping them up into myelin sheaths (activation in OL and other glia cells).
After Rho’s activation, which is partly mediated from myelin associated glycoproteins, there must be additional influx of calcium into the neuron (and glia cells) at once, to serve further Rho’s actions. The amount of calcium depends on amount of activated Rho, the regulation goes by demand. Under normal circumstances this amount will never go over the physiological limit, otherwise the structural development and constant repair of the brain tissue will be simply impossible. Rho’s never go ‘after’ the neuron’s body, they work on compartmental level only.
The extended time of survival in the neurons under extreme conditions, when Rho’s were inhibited, was depended on this ‘Rho assigned’ amount of calcium which was eliminated from total quantity of calcium influx/entry.
Keep in mind, when Rho’s are inhibited, the chain of further events associated with Rho is halted, and these events are calcium depended also. The intracellular calcium under this condition will be much lower than usual when the stress was applied.
In other words, in this study we have weak and delayed response of neurons to applied over-stress, and, of course, these neurons will last longer. But this has nothing to do with real life event – cell death.
That’s why Rho’s activation alone could not be considered as “brand new pathway of cell death”, it is technically incorrect. It is not even ‘new’, it is any.
Apoptosis is pretty complex, and I don’t think that it is correct to pick up the separate part of the whole process and claim its entire responsibility for neuronal death. It wouldn’t happen unless you have an idea to promote the compound which inhibits Rho.
In addition, it was shown that the Rho-kinase inhibitor only partially prevented axonal degeneration in brain; this confirms that other factors were participated (and actually caused the total axonal degeneration with following neuronal death).
Also, the attempts to detect activation of Rho in the injured axons following sciatic nerve transection have failed. There is a question: how it could be possible, that in this pretty complicated situation, when neuron’s body located within spinal cord (a part of CNS) and has the very long (leg’s long) axon and therefore is more vulnerable and dependent of the inner structure, this “brand new pathway of cell death” is not being deployed?
Take a guess.
"All truth passes through three stages.
First it is ridiculed.
Second it is violently opposed.
Third it is accepted as being self-evident."