Zebra fish and Parkinson’s …..a possible genetic screening model?

The primary symptoms of Parkinson’s disease include slowness of movement, postural instability, impaired balance. While there are also non motor symptoms of PD, it predominantly affects motor function. Diagnosis of Parkinson’s disease is purely based on neurological symptoms and medical history. The result of all this is that there is no current cure for Parkinson’s disease and all the current treatments are limited to treating the symptoms of Parkinson’s disease . While 85-90% of PD cases are sporadic about 10-15% have a familial predisposition. Hence, characterizing the various genes involved in sporadic PD is largely unexplored and warrants further investigation. Zebra fish is a highly effective model for studying human diseases due to its fast external development, short generation times and that several cellular processes have been conserved through vertebrate evolution.Mutating the entire genome and looking for phenotypes of contractile dysfunction has already been done in zebra fish. With the advent of video tracking technology, we can induce mutations in the entire genome and look for Parkinson’s like symptoms such as locomotive impairment and turn angle performance in zebra fish. By mapping and sequencing of these mutant zebra fish genomes we can look for novel genes that might be involved in Parkinson’s disease. A comparative model with Parkinson’s like phenotypes after 7 dpf and 3 months post fertilization could give us a pattern of neuronal dysfunction. It might be reasonable to suggest that no particular candidate gene exists and hence PD is likely to be caused by a combination of several, yet to be identified, genetic factors. Secondly, LRRK2 is a gene recently found to have been involved in Parkinson’s disease and mutations in LRRK2 have been known to cause cell death in neurons. LRRK2 is a leucine rich repeat kinase and it has been found that LRRK2 mutations in Zebra fish can be rescued by injecting a wild type human or zebra fish copy of the gene. Hence, we could use the mutant rescue model to recover all mutant phenotypes in this Parkinson’s model. Also, chemically reactive species containing oxygen called reactive oxygen species have known to cause cell damage as they increase during oxidative stress. Oxidative stress has been implicated in dopamine cell degeneration and we aim to study the effect of oxidative stress in these mutant zebra fish. Several phenotypes caused by genes implicated in Parkinson’s disease can be partially recovered by the administering a monoamine oxidase inhibitor. Hence, to study which mutant phenotypes are enhanced by oxidative stress could be a key finding in the treatment of PD.

Advertisements