Journal Article

Parkin promotes intracellular Aβ<sub>1–42</sub> clearance

Mark P. Burns, Lihua Zhang, G. William Rebeck, Henry W. Querfurth and Charbel E.-H. Moussa

in Human Molecular Genetics

Volume 18, issue 17, pages 3206-3216
Published in print September 2009 | ISSN: 0964-6906
Published online May 2009 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddp258
Parkin promotes intracellular Aβ1–42 clearance

Show Summary Details

Preview

Alzheimer's disease and Parkinson's disease are common neurodegenerative diseases that may share some underlying mechanisms of pathogenesis. Aβ1–42 fragments are found intracellularly, and extracellularly as amyloid plaques, in Alzheimer's disease and in dementia with Lewy Bodies. Parkin is an E3-ubiquitin ligase involved in proteasomal degradation of intracellular proteins. Mutations in parkin, which result in loss of parkin function, lead to early onset Parkinsonism. Here we tested whether the ubiquitin ligase activity of parkin could lead to reduction in intracellular human Aβ1–42. Lentiviral constructs encoding either human parkin or human Aβ1–42 were used to infect M17 neuroblastoma cells. Parkin expression resulted in reduction of intracellular human Aβ1–42 levels and protected against its toxicity in M17 cells. Co-injection of lentiviral constructs into control rat primary motor cortex demonstrated that parkin co-expression reduced human Aβ1–42 levels and Aβ1–42-induced neuronal degeneration in vivo. Parkin increased proteasomal activity, and proteasomal inhibition blocked the effects of parkin on reducing Aβ1–42 levels. Incubation of Aβ1–42 cell lysates with ubiquitin, in the presence of parkin, demonstrated the generation of Aβ–ubiquitin complexes. These data indicate that parkin promotes ubiquitination and proteasomal degradation of intracellular Aβ1–42 and demonstrate a protective effect in neurodegenerative diseases with Aβ deposits.

Journal Article.  6357 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.