Parkinson's gene

Print edition : January 05, 2018

Muhammad Ali (here with daughter Laila Ali) battled Parkinson’s disease. A new study finds the role of a particular gene in late-onset Parkinson’s disease. Photo: MICHAEL HICKEY/AFP

FOR more than a decade, scientists have known that certain mutations in a gene called LRRK2 are the most common genetic cause for late-onset Parkinson’s disease, a progressive disorder in which neurons in the brain are lost over several years. But the exact mechanism was hitherto unknown. Significantly, in certain Asian populations, specific variants of LRRK2 are known to lower the age of onset.

Now a team of researchers led by the neuroscientist Sandhya Koushika at the Tata Institute of Fundamental Research (TIFR) in Mumbai has identified a critical role for the gene in the brain. Their study, published in the journal PLoS Genetics, shows that LRRK2 is vital for the formation of synaptic vesicles, membranous bags that carry neurotransmitters whose release allows movement and other motor activities. According to the scientists, the ability to fill neurotransmitters and function depends absolutely on the composition of these vesicles.

Using roundworm as an experimental model, Sandhya Koushika and her colleagues demonstrated that the LRRK2 gene forms a protein complex along with another gene, JIP3, which acts as an assembly line to form a synaptic vesicle. This assembly line first removes unnecessary proteins from the membrane compartment following which LRRK2 acts to include the right proteins. Finally, a specific motor which powers the movement of the vesicle to the correct destination is attached, the study found. Improperly formed synaptic vesicles lead to impaired neuron function and inability to release neurotransmitters and thereby trigger defects in movement.

The study provides insights into what might go wrong in some forms of Parkinson’s, and this understanding may help find better treatment. Parkinson’s disease currently has no cure, and the treatment currently focusses on symptomatic relief, which fails to have an impact as the disease progresses.

T.V. Jayan