Research on Parkinson’s disease

18 October 2018

NZORD awarded the best poster prize at the Queenstown Research Week Satellite on Rare Brain Diseases meeting in August to Marie Isabelle Viola, a Masters student from the National Institute of Molecular Biology, University of Philippines Diliman. She completed her research on a rare form of Parkinson’s disease which is endemic to the Philippines. This rare form is linked to cell proliferation (rapid division), so this research may have benefits for future cancer treatments as that is also related to cell proliferation.

Here is an overview of the research:

Preliminary investigations on the functionality of INGX, a pseudogene found in the XDP (X-linked Dystonia Parkinsonism) locus

Viola, M.1, Garcia, R.1

1National Institute of Molecular Biology and Biotechnology, University of the Philippines Diliman, Metro Manila, PH

X-linked Dystonia Parkinsonism (XDP; Lubag) is a rare middle-onset neurodegenerative disorder almost exclusive to males of Filipino descent. Dystonia manifests during the third decade of life and progresses to Parkinsonism within approximately the next decade. Neuropathology of XDP patient brains exhibits severe neuronal loss and astrogliosis. The XDP disease locus has been mapped to Xq13.1 spanning a TAF1/DYT3 multiple transcript system with a haplotype of 5 disease-specific mutations, an SVA insertion, and a 48-bp deletion. TATA-box binding protein 1 (TAF1), a crucial initiator of transcription, is said to be the main causative gene due to the observed downregulation of its neuronal specific isoform, N-TAF1, in patient brains. However, investigation of other genetic lesions that may cause the severe progressive biphasic nature of XDP is warranted. Often overlooked is INGX, an annotated pseudogene antisense to the region of the TAF1/DYT3 transcript. Its function is unknown. ING1, its functional counterpart, is a well-studied tumour suppressor with vast regulatory functions in cellular proliferation, apoptosis and senescence. It was thus imperative to establish that INGX is a functional pseudogene as a prelude to understanding its possible roles in cancer and neuronal cells. Gene expression profiling of INGX across cancer and normal tissues and cell lines via data mining and quantitative PCR revealed tissue specific expression - characteristic of a functional pseudogene. Investigations on the phenotypic consequences of INGX overexpression and knockdown in cancer and neuronal cells using various hallmark assays common to both cancer and neurodegeneration including proliferation, apoptosis, and migration, are underway.