Valted, LLC

Jooho Shin

Ted M Dawson

Valina L Dawson

Han Seok Ko

Parkinson's disease is caused by the preferential loss of substantia nigra dopamine neurons. A Parkin Interacting Substrate, PARIS (ZNF746) is identified. The levels of PARIS are regulated by the ubiquitin proteasome system via binding to and ubiquitination by the E3 ubiquitin ligase, parkin. PARIS is a KRAB and zinc finger protein that accumulates in models of parkin inactivation and in human brain Parkinson's disease patients. PARIS represses the expression of the transcriptional co-activator, PGC-1&#x3b1; and the PGC-1&#x3b1; target gene, NRF-1 by binding to insulin response sequences in the PGC-1&#x3b1; promoter. Conditional knockout of parkin in adult animals leads to progressive loss of dopamine (DA) neurons that is PARIS dependent. Overexpression of PARIS causes selective loss of DA neurons in the substantia nigra, which is reversed by either parkin or PGC-1&#x3b1; co-expression. The identification of PARIS provides a molecular mechanism for neurodegeneration due to parkin inactivation.

Growing community of inventors

Ellicott City, MD, United States of America

Jooho Shin