Written by Joyce Smith, BS. This study demonstrates how a defective gene (PLA2g6) plays an important role in the development of idiopathic Parkinson’s disease.
Parkinson’s disease (PD) is a progressive disorder of the nervous system that affects more than one million people in North America and more than four million people worldwide. It involves the malfunction and death of vital nerve cells in an area of the brain known as the substantia nigra. Normally, these nerve cells, or neurons, produce a chemical messenger called dopamine, which transmits signals to the part of the brain that controls movement and coordination. (1-4)
The first symptoms of Parkinson’s are often trembling or shaking of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other characteristic symptoms include rigidity or stiffness of the limbs and torso, slow movement or an inability to move and impaired balance and coordination. These symptoms worsen slowly over time. (1-4) There is currently no effective treatment that avoids, delays, or halts the progression of the neurodegenerative effects of this disease.
When researchers analyzed the brain cells from patients with idiopathic PD, they discovered a defective gene protein (PLA2g6) that interferes with the normal functioning of calcium in the body. This genetic dysfunction of calcium signaling triggers a sequence of pathological events in which autophagic dysfunction (self-digestion of cells) occurs, dopamine-producing neurons die and age-dependent vital motor functions are lost. 1-4
Researchers were then able to mimic this deficiency in PLA2g6 – dependent calcium signaling in a mouse model. They used a wide array of genetic, molecular, cellular, imaging behavior and other approaches for in vivo and in vitro studies in human cells and a mouse model. By monitoring aging PLAg6 mice and wild mice (controls) for signs and severity of clinical symptoms, they were able to demonstrate the following:
- There was progressive loss of dopaminergic neurons and age-dependent PD –like motor dysfunction in PLA2g6 mice in balance beam, pole, rotarod and grip tests P<0.01, P<0.001 but not in wild-type control mice.
- When brains were immunostained and analyzed, a causal link was found between PLA2g6 mice and autophagic dysfunction P<0.05, P<0.001
- These PLA2g6 mice manifested the same calcium-impaired signaling and loss of dopaminergic neurons and age –related motor function as seen in human idiopathic PD. P<0.01
The researchers concluded that genetic impairment of PLA2g6 –dependent calcium signaling is a trigger for autophagic dysfunction, progressive loss of dopaminergic neurons and age-dependent motor function loss in idiopathic Parkinson’s disease.
Source: Zhou, Q. et al. Impairment of PARK14-dependent Ca2þ signalling is a novel determinant of Parkinson’s disease. Nat. Commun. 7:10332 doi: 10.1038/ncomms10332 (2016).
© Creative Commons Attribution 4.0 International License.
Click here to read the full text study.
Posted February 29, 2016.
References:
- Trinh J, Farrer M. Advances in the genetics of Parkinson disease. Nature Reviews Neurology. 2013;9(8):445-454.
- Antony P, Diederich NJ, Krüger R, Balling R. The hallmarks of Parkinson’s disease. FEBS Journal. 2013;280(23):5981-5993.
- Dexter DT, Jenner P. Parkinson disease: from pathology to molecular disease mechanisms. Free Radical Biology and Medicine. 2013;62:132-144.
- Obeso JA, Rodriguez-Oroz MC, Goetz CG, et al. Missing pieces in the Parkinson’s disease puzzle. Nature medicine. 2010;16(6):653-661.
