RGD Reference Report - Prostate apoptosis response-4 production in synaptic compartments following apoptotic and excitotoxic insults: evidence for a pivotal role in mitochondrial dysfunction and neuronal degeneration.

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Prostate apoptosis response-4 production in synaptic compartments following apoptotic and excitotoxic insults: evidence for a pivotal role in mitochondrial dysfunction and neuronal degeneration.
Authors:	Duan, W Rangnekar, VM Mattson, MP
Citation:	Duan W, etal., J Neurochem. 1999 Jun;72(6):2312-22.
RGD ID:	9835366
Pubmed:	PMID:10349840 (View Abstract at PubMed)
Synapses are often located at great distances from the cell body and so must be capable of transducing signals into both local and distant responses. Although progress has been made in understanding biochemical cascades involved in neuronal death during development of the nervous system and in various neurodegenerative disorders, it is not known whether such cascades function locally in synaptic compartments. Prostate apoptosis response-4 (Par-4) is a leucine zipper and death domain-containing protein that plays a role in neuronal apoptosis. We now report that Par-4 levels are rapidly increased in cortical synaptosomes and in dendrites of hippocampal neurons in culture and in vivo, following exposure to apoptotic or excitotoxic insults. Par-4 expression is regulated at the translational level within synaptic compartments. Par-4 antisense treatment suppressed mitochondrial dysfunction and caspase activation in synaptosomes and prevented death of cultured hippocampal neurons following exposure to excitotoxic and apoptotic insults. Local translational regulation of death-related proteins in synaptic compartments may play a role in programmed cell death, adaptive remodeling of synapses, and neurodegenerative disorders.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
PAWR	Human	epilepsy		ISO	RGD:69065	protein:increased expression:hippocampus:	RGD
Pawr	Rat	epilepsy		IEP		protein:increased expression:hippocampus:	RGD
Pawr	Mouse	epilepsy		ISO	RGD:69065	protein:increased expression:hippocampus:	RGD

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Biological Process

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Pawr	Rat	positive regulation of intrinsic apoptotic signaling pathway		IMP			RGD
Pawr	Rat	response to iron(II) ion		IEP			RGD

Cellular Component

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Pawr	Rat	neuronal cell body		IDA			RGD

Objects Annotated

Genes (Rattus norvegicus)

Pawr (pro-apoptotic WT1 regulator)

Genes (Mus musculus)

Pawr (PRKC, apoptosis, WT1, regulator)

Genes (Homo sapiens)

PAWR (pro-apoptotic WT1 regulator)

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Prostate apoptosis response-4 production in synaptic compartments following apoptotic and excitotoxic insults: evidence for a pivotal role in mitochondrial dysfunction and neuronal degeneration.