engleski

Elucidating the putative role of alpha-synuclein in transcription

The contribution of transcriptional dysregulation to neurodegeneration has been studied in multiple models of neurodegenerative diseases. Molecular mechanisms of transcriptional dysregulation have recently become a focus of attention in Parkinson’s disease (PD) as well. Altered gene expression has been detected both peripherally, in blood cells, and more locally, in dopaminergic substantia nigra neurons in PD patients, as well as in mouse models of the disease. Moreover, the presence of alpha-synuclein in the nucleus has remained unclear, although some studies suggest it promotes neurotoxicity when present in this compartment, by modulating the levels of acetylated histone H3. In an effort to elucidate the role of alpha-synuclein in the nucleus and its potential effect on transcription, which could yield novel clues into the pathways involved in neurotoxicity, we tried to identify transcriptional targets of wild-type and mutated alpha-synuclein, which is responsible for development of genetic forms of Parkinson’s disease. Using the approach of chromatin immunoprecipitation coupled with next-generation sequencing, we identified possible genomic targets of mutated alpha-synuclein. The results of the study identified a large number of both wild-type and mutated alpha-synuclein, affecting such diverse sets of genes as protein degradation, miRNA processing and genes pertaining to the NF-KAPPA B complex. In conclusion, location analysis of wild type and mutated alpha-synuclein may give insight into pathological mechanisms involved in neurodegenerative diseases.

alpha-synuclein; genomics; Parkinson's disease

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