Work

Decreases in valosin-containing protein result in increased levels of tau phosphorylated at Ser262/356

Year: 2011

Type: article

Abstract: VCP/p97 is a multifunctional AAA+-ATPase involved in vesicle fusion, proteasomal degradation, and autophagy. Reported dysfunctions of these processes in Alzheimer disease (AD), along with the linkage of VCP/p97 to inclusion body myopathy with Paget's disease and frontotemporal dementia (IBMPFD) led us to examine the possible linkage of VCP to the AD-relevant protein, tau. VCP levels were reduced in AD brains, but not in the cerebral cortex of an AD mouse model, suggesting that VCP reduction occurs upstream of tau pathology. Genetic reduction of VCP in a primary neuronal model led to increases in the levels of tau phosphorylated at Ser(262/356), indicating that VCP may be involved in regulating post-translational processing of tau in AD, demonstrating a possible functional linkage between tau and VCP.

Source: FEBS Letters

DOI: 10.1016/j.febslet.2011.09.032

Authors: Philip J. Dolan, Youngnam N. Jin, Woong Hwang, Gail V.W. Johnson

Institutions: University of Alabama at Birmingham, University of Rochester, University of Rochester Medicine

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Physiology (medical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Alzheimer's Association, National Institutes of Health, National Institute of Neurological Disorders and Stroke