BAG5 Inhibits Parkin and Enhances Dopaminergic Neuron Degeneration

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BAG5 Inhibits Parkin and Enhances Dopaminergic Neuron Degeneration

Loss-of-function mutations in the parkin gene, which encodes an E3 ubiquitin ligase, are the major cause of early-onset Parkinson's disease (PD). Decreases in parkin activity may also contribute to neurodegeneration in sporadic forms of PD. Here, we show that bcl-2-associated athanogene 5 (BAG5), a BAG family member, directly interacts with parkin and the chaperone Hsp70. Within this complex, B...

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Drosophila overexpressing parkin R275W mutant exhibits dopaminergic neuron degeneration and mitochondrial abnormalities.

Mutations in the parkin gene are a predominant cause of familial parkinsonism. Although initially described as a recessive disorder, emerging evidence suggest that single parkin mutations alone may confer increased susceptibility to Parkinson's disease. To better understand the effects of parkin mutations in vivo, we generated transgenic Drosophila overexpressing two human parkin missense mutan...

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Parkin and Hsp70 Sacked by BAG5

Loss-of-function mutations in the parkin gene, which encodes an E3 ubiquitin ligase, are the major cause of early-onset Parkinson's disease (PD). In this issue of Neuron, Kalia et al. show that the bcl-2-associated athanogene 5 (BAG5) enhances dopamine neuron death in an in vivo model of PD through inhibiting the E3 ligase activity of parkin and the chaperone activity of Hsp70.

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Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration.

Parkin and the glial cell line-derived neurotrophic factor (GDNF) receptor RET have both been independently linked to the dopaminergic neuron degeneration that underlies Parkinson's disease (PD). In the present study, we demonstrate that there is genetic crosstalk between parkin and the receptor tyrosine kinase RET in two different mouse models of PD. Mice lacking both parkin and RET exhibited ...

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Parkin Suppresses Dopaminergic Neuron-Selective Neurotoxicity Induced by Pael-R in Drosophila

Parkin, an E3 ubiquitin ligase that degrades proteins with aberrant conformations, is associated with autosomal recessive juvenile Parkinsonism (AR-JP). The molecular basis of selective neuronal death in AR-JP is unknown. Here we show in an organismal system that panneuronal expression of Parkin substrate Pael-R causes age-dependent selective degeneration of Drosophila dopaminergic (DA) neurons...

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ژورنال

عنوان ژورنال: Neuron

سال: 2004

ISSN: 0896-6273

DOI: 10.1016/j.neuron.2004.11.026