Implications for the Amgen aborted study?

http://www.eurekalert.org/pub_releas...-ntf071608.php
Neuronal Death Path
Li-ying Yu, Mart Saarma, and Urmas Arumäe

Programmed cell death pathways are generally divided into two broad categories: the intrinsic pathway, in which cellular stress (e.g., oxidative stress) leads to release of cytochrome c from mitochondria, which leads to activation of caspase-9, which activates effector caspases that degrade cellular proteins; and the extrinsic pathway, in which extracellular ligands bind to death receptors, which activate Fas-activated death domain (FADD) protein, which leads to activation of caspase-8, which activates effector caspases. This week, Yu et al. describe the apoptosis pathway activated by withdrawal of GDNF and BDNF from cultured midbrain dopaminergic neurons. The normal intrinsic pathway was not involved, because cytochrome c was not released from mitochondria. Nonetheless, caspase-9 was involved. Death-receptor pathways were also involved, because blocking FADD or caspase-8 prevented apoptosis. Interestingly, this apoptosis pathway is different than that induced by withdrawal of GDNF from sympathetic neurons.

Madelyn,
In a few words to answer your question about implications - I would think so. The abrupt withdrawal of GDNF has been argued to have been the cause of the infamous monkey lesions. But the dosage was extremely high.

Am I under the correct assumption to interpret this article as implying that withdrawal of GDNF could have increased neuronal death in the participants?

paula

I only read that the pathway of apoptosis (cell death) is "different" from the natural path of destruction when GDNF deprivation is introduced.

I didn't have time to extensively check out this researcher, but here is the latest abstract from Pub Med:
I think this just says they found a new way to look at the proteins and neurons involved in cell death in dopaminergic neurons by depriving them GDNF. This cell death thing (apoptosis) is heavy technical stuff, but here's a poster for those of you who can read the language:
http://www.emdbiosciences.com/docs/d...s_poster_E.pdf

As I see it, the benefit of what these authors have found could be very helpful in stem cell research and gene therapy (among other strategies studied).