I remember it like it was yesterday. I woke up to the phone ringing at 3AM on a Thursday night. It was Grandma again, asking for a ride to church. My dad tried to explain that church wasn’t for another few days, plus it was the middle of the night, but it wouldn’t sink in. Within a year Grandma would be moved to a home that specialized in memory loss care, after doctors suspected that Alzheimer’s Disease had begun to clutter her mind.
Alzheimer’s Disease is characterized by the aggregation of Amyloid-beta protein plaques in the brain. For many years researchers were unsure of exactly what the plaques had to do with the memory loss and neurodegeneration doctors were observing in their patients like my grandma. But the most recent research has discovered a mechanism in the brain that just might be the missing piece to the puzzle. This mechanism, called the PI3-Akt pathway, is activated by insulin and another protein called insulin-like growth factor. This pathway has demonstrated great promise in Alzheimer’s research, as reducing its activation has been shown to expand healthy lifespan. In addition, sustained activation of the system has been recognized in the brains of those afflicted by Alzheimer’s Disease. Scientists now hypothesize that it is the aggregation of the Amyloid-beta plaques that may be interfering with the PI3-Akt signaling pathway and its activation by insulin. As a result, current therapeutic approaches are aimed at attempting to normalize this signaling pathway.
While researchers attempt to find the shut-off for the PI3-Akt pathway, other options such as Lumosity and other brain training games claim to slow the progression of memory loss. But are these alternatives truly effective? Although clearly not a cure, these exercises have been shown to help improve memory and cognitive function. But with a disease such as Alzheimer’s that manifests itself in so many different forms in its victims, it’s hard to say exactly how much of an impact Lumosity and others are able to make.
Grandma can’t walk anymore or talk much, only the occasional mumbled greeting when I show up to visit after being away at college. I’m not sure if she even knows who I am at this point. She remains in the home, where she will likely spend the rest of her life. It’s been a rough journey, and I pray that Grandma is still in there somewhere. All I can do is hope anyway, for that and for a cure for the disease that has stolen away grandparents from so many.
The Thief in the Night: Alzheimer's Disease
It is the opposite. While overactivation of the PI3-Akt kinase can contribute to cancer; in Alzheimer’s disease its inhibition contributes to neurodegeneration (reduced blood flow in the brain, the formation of tau tangles that may interfere with neurotransmissions, and an end to the regeneration of neurons in the hippocampus.
Two distinct signaling pathways regulate peroxynitrite-induced apoptosis in PC12 cells
Edited by M Miura
J J Shacka1,6, M A Sahawneh2, J D Gonzalez1, Y-Z Ye1,7, T L D’Alessandro3 and A G Estévez1,4,5,7
The mechanisms of peroxynitrite-induced apoptosis are not fully understood. We report here that peroxynitrite-induced apoptosis of PC12 cells requires the simultaneous activation of p38 and JNK MAP kinase, which in turn activates the intrinsic apoptotic pathway, as evidenced by Bax translocation to the mitochondria, cytochrome c release to the cytoplasm and activation of caspases, leading to cell death. Peroxynitrite induces inactivation of the Akt pathway. Furthermore, overexpression of constitutively active Akt inhibits both peroxynitrite-induced Bax translocation and cell death. Peroxynitrite-induced death was prevented by overexpression of Bcl-2 and by cyclosporin A, implicating the involvement of the intrinsic apoptotic pathway. Selective inhibition of mixed lineage kinase (MLK), p38 or JNK does not attenuate the decrease in Akt phosphorylation showing that inactivation of the Akt pathway occurs independently of the MLK/MAPK pathway. Together, these results reveal that peroxynitrite-induced activation of the intrinsic apoptotic pathway involves interactions with the MLK/MAPK and Akt signaling pathways.
Alzheimer’s disease can be treated with peroxynitrite scavengers such as rosemary and other essential oil containing eugenol via aromatherapy (Jimbo, 2009), lemon balm extract (Akhondzadeh, 2004), and panax ginseng (Heo 2011, 2012).
I am sorry for you and your grandmother. My mother had Alzheimer’s disease for 8 years (before dying of heart failure). She did considerably better after we began aromatherapy.