Редактирование: BLVRA (раздел)

==Publications==

{{medline-entry
|title=Attenuation of epigenetic regulator [[SMARCA4]] and ERK-ETS signaling suppresses aging-related dopaminergic degeneration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32749068
|abstract=How complex interactions of genetic, environmental factors and aging jointly contribute to dopaminergic degeneration in Parkinson's disease (PD) is largely unclear. Here, we applied frequent gene co-expression analysis on human patient substantia nigra-specific microarray datasets to identify potential novel disease-related genes. In vivo Drosophila studies validated two of 32 candidate genes, a chromatin-remodeling factor [[SMARCA4]] and a biliverdin reductase [[BLVRA]]. Inhibition of [[SMARCA4]] was able to prevent aging-dependent dopaminergic degeneration not only caused by overexpression of [[BLVRA]] but also in four most common Drosophila PD models. Furthermore, down-regulation of [[SMARCA4]] specifically in the dopaminergic neurons prevented shortening of life span caused by α-synuclein and [[LRRK2]]. Mechanistically, aberrant [[SMARCA4]] and [[BLVRA]] converged on elevated ERK-ETS activity, attenuation of which by either genetic or pharmacological manipulation effectively suppressed dopaminergic degeneration in Drosophila in vivo. Down-regulation of [[SMARCA4]] or drug inhibition of MEK/ERK also mitigated mitochondrial defects in [[PINK1]] (a PD-associated gene)-deficient human cells. Our findings underscore the important role of epigenetic regulators and implicate a common signaling axis for therapeutic intervention in normal aging and a broad range of age-related disorders including PD.

|keywords=* 
Drosophila

* MAPK-ERK-ETS signaling
* Parkinson's disease
* SMARCA4/Brahma
* aging
* neurodegeneration
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511865
}}