Although the root cause of Parkinson's Disease (PD) is still a mystery, a recent study finds a protective mechanism against Lewy bodies, the abnormal protein aggregates related to PD.
Parkinsonism affects motor functions of the body and is a result of the destruction of the substantia nigra in the brain. The substantia nigra, a part of the basal ganglia, is responsible for producing dopamine and inhibiting glutamate and GABA (gamma-Aminobutyric acid) in the corpus striatum. The uninhibited striatum causes the classic tremor and motor skill impairment seen in patients with Parkinson’s disease.
Abnormal protein aggregates that appear as dense eosinophillic masses called Lewy bodies accumulate in regions of the substanta nigra where dopaminergic neurons are destroyed. These protein aggregates are suggested to play a part in the pathogenesis of Parkinson’s disease.
Over the decades, scientists have established a correlation between dopaminergic neurons and the mitochondria of these cells. A study conducted by the Department of Neurology, Juntendo University School of Medicine, Tokyo in 1989 found that immunoblotting results on mitochondria of the basal ganglia showed a deficiency in the mitochondrial enzyme, Complex I.
After immense follow-up research on this study, it was theorized that perhaps the decreased levels of Complex I in the mitochondria of the substantia nigra was an important cause of Parkinsonism.
However, the latest study conducted in late December 2017 came up with a slightly different approach to this theory. A research led by the Department of Clinical Medicine UiB investigated the brain tissue of 18 subjects that had Parkinsonism and compared it with the brain tissue of 11 people who did not.
The first interesting fact they observed was that patients with Parkinsonism had reduced Complex I levels throughout the entire brain. Had Complex I played a role in the pathogenesis of PD, its levels would have been reduced only in the cells of the substantia nigra.
Another important discovery made during this research was that the mitochondria of cells that had low levels of the Complex 1 enzyme, in fact, had little or no Lewy bodies in them.
These conclusions suggest that the reduced levels of Complex I might actually be a part of a protective mechanism by the body against the abnormal Lewy bodies. With this groundbreaking research, it is possible that we are one step closer to discovering the root cause of PD and producing drugs that can hopefully treat the condition for good.
Flønes, I.H., Fernandez-Vizarra, E., Lykouri, M. et al. Acta Neuropathol (2017). https://doi.org/10.1007/s00401-017-1794-7