Objective: To scan the human genome for genes involved in neuronal health maintenance in Parkinson’s disease (PD).

Background: An enormous number of genes and pathways have been found to be associated with PD which makes it difficult to understand its pathogenesis. A whole genome approach to understand the etiopathogenesis of PD seems to hold promise.

Methods: Many databases and softwares were used to make a complete gene list associated with PD. All these enlisted genes were then classified on the basis of their function. An enrichment analysis was also carried out (False Detection Rate <0.001) which revealed 42 different pathways. Further scanning was done on the genes to be significantly associated with neuronal viability maintenance which revealed 14 genes. Then functional analysis was carried out on these genes.

Results: The 42 pathways to be significantly associated with PD pathogenesis spread over many domains including apoptosis, cell cycle regulation, mitochondrial function, inflammation, calcium signaling, angiogenesis etc. The 14 genes found to be associated significantly with neuron maintenance in PD were involved in neurotrophin signaling pathway. They are BAD (Apoptosis), BDNF (Neurotrophin),CASP3 (Apoptosis),CDKN1A (Cell cycle regulation),CDKN1B (Cell cycle progression),LINGO1 (Axonal regeneration),MAPK3 (Cell proliferation/differentiation),NFKB1 (Transcription regulator),NGF (Nerve growth),NGFR (Nerve Growth),NTF3 (Neuronal Survival),NTRK1 (Cell differentiation),NTRK2 (Cell differentiation), TP53 (Apoptosis/senescence). Functional analysis of these genes revealed that they operate in a network as an on/off switch for apoptosis and inflammation.

Conclusions: Pathogenecity progression in Parkinson’s disease may be a combination of many pathways but the central events involved in dysregulation of neuronal health may be neurotrophin signaling pathway. Proper neurotrophin based intervention may help in preventing the onset and developing novel treatment regimens for PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genome-wide-bioinformatic-analysis-of-parkinsons-disease-a-focus-on-neuronal-health-maintenance/