Abstract: Research into neuroprotective mechanisms has at its heart the goal of developing new therapeutic strategies to treat patients. For example, the compositions and induction strategies disclosed herein have use for acute injuries such as stroke or trauma, and would be extremely useful in treating patients undergoing cardiac bypass surgery, neurosurgery or other surgical cohorts where ischemia is a risk. Further, patients with subarachnoid hemorrhage, transient ischemic attacks, soldiers at risk for blast injury or patients suffering from chronic neurodegenerative diseases would also benefit from enhanced neuronal survival based upon the techniques and compositions disclosed herein. In addition, protecting against cell death by, for example, interfering with PAR polymer signaling via the compositions and processes disclosed herein, offers new therapeutic strategies for the treatment of neurologic disorders.

Abstract: 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? and the PGC-1? target gene, NRF-1 by binding to insulin response sequences in the PGC-1? 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? co-expression. The identification of PARIS provides a molecular mechanism for neurodegeneration due to parkin inactivation.

Abstract: 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? and the PGC-1? target gene, NRF-1 by binding to insulin response sequences in the PGC-1? 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? co-expression. The identification of PARIS provides a molecular mechanism for neurodegeneration due to parkin inactivation.

Abstract: 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? and the PGC-1? target gene, NRF-1 by binding to insulin response sequences in the PGC-1? 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? co-expression. The identification of PARIS provides a molecular mechanism for neurodegeneration due to parkin inactivation.

Abstract: 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? and the PGC-1? target gene, NRF-1 by binding to insulin response sequences in the PGC-1? 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? co-expression. The identification of PARIS provides a molecular mechanism for neurodegeneration due to parkin inactivation.

Abstract: 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? and the PGC-1? target gene, NRF-1 by binding to insulin response sequences in the PGC-1? 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? co-expression. The identification of PARIS provides a molecular mechanism for neurodegeneration due to parkin inactivation.