In recent years, researchers have speculated that certain neurons believed to be dead during neurodegenerative diseases are actually in a dormant state. Researchers led by Dr. C. Justin Lee, Dr. Hoon Ryu, and Dr. Sang Ryong Jeon, have reported that symptoms of Parkinson's disease appear when dopaminergic neurons become "nonfunctional" , long before they die.
Although neuronal death has so far been considered the obvious cause of Parkinson's disease, the study found that motor abnormalities begin at the earlier stage when dopaminergic neurons begin to be unable to synthesize dopamine.
"Everyone agrees with the conventional idea that neuronal death is the sole cause of Parkinson's disease. This hampers efforts to investigate other neuronal states, such as the influence that surrounding astrocytes can have "said Dr. C. Justin Lee.
He adds: "Neuronal death has ruled out any possibility of reversing the course of Parkinson's disease. But as it is now shown that dormant neurons can be awakened to resume their productive capacity, this discovery gives patients with Parkinson's disease hope for a cure. "
The appearance of reactive astrocytes is an important characteristic not only of Parkinson's disease, but also of many other brain diseases, including AD, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, brain damage traumatic and stroke. However, it was recognized that the role of these reactive astrocytes was limited to neuroinflammation or metabolic support. The study by Korean researchers suggests that the interaction between astrocytes and neurons via the powerful inhibitory gliotransmitter GABA, is a critical factor in the progression of Parkinson's disease. They confirmed that dormant dopaminergic neurons are alive and can be awakened by treatment with inhibitors of Monoamine oxidase B, which block the astrocytic synthesis of GABA.
Monoamine oxidase B (MAO-B) is an enzyme located in the outer mitochondrial membrane. It plays an important role in the catabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. This protein preferentially degrades benzylamine and phenylethylamine, and also dopamine
However, the results of several clinical trials have questioned the therapeutic efficacy of traditional irreversible MAO-B inhibitors such as selegiline and rasagiline. Long-term use of irreversible MAO-B inhibitors undesirably activates the compensatory mechanisms of GABA production.
Korean researchers recently developed a new class of Monoamine oxidase inhibitor, KDS2010, which effectively inhibits the astrocytic synthesis of GABA to completely save neurons, with minimal side effects in animal models of Alzheimer's disease. They believe that this new compound will also be effective in relieving parkinsonian motor symptoms in animal models as well as in patients with Parkinson's disease.
