JCI table of contents: April 22, 2008

Consistent with previous studies, it was found that elimination of Pin1 in mice enhanced the stability of nonmutated tau protein, whereas overexpression of Pin1 decreased the stability of the protein and suppressed tauopathy in mice engineered to express nonmutated human tau. By contrast, elimination of Pin1 in mice decreased the stability of P301L tau and suppressed tauopathy in mice engineered to express P301L tau, whereas overexpression of Pin1 enhanced tauopathy in P301L tau mice. The authors therefore suggest that therapeutics inducing Pin1 up-regulation might be beneficial for individuals with AD, whereas Pin1 inhibition might be helpful for patients with FTDP-17 due to P301L tau.

TITLE: Pin1 has opposite effects on wild-type and P301L tau stability and tauopathy

AUTHOR CONTACT:
Kun Ping Lu
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Phone: (617) 667-4143; Fax: (617) 667-0610; E-mail: .

MEDIA CONTACT:
Bonnie Prescott
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Phone: (617) 667-7306; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=34308

VIROLOGY: Uncovering the secret ways of HIV: the HIV protein Nef impairs blood cell development

The generation and function of all types of blood cell are impaired in individuals infected with HIV. HIV is thought to cause this problem by disrupting the function of cells that are the precursors of all blood cells; these cells are known as hematopoietic progenitor cells. Exactly how HIV affects hematopoietic progenitor cells has not been determined, although it seems to be an indirect effect as the cells are not themselves infected with HIV. New data, generated by Stéphane Prost and colleagues, at the Institute of Emerging Disease and Innovative Therapies, CEA, France, have now indicated that the HIV protein Nef disrupts the function of hematopoietic progenitor cells.

In the study, production of the protein Nef was shown to be essential for the monkey form of HIV (SIV) to disrupt hematopoietic progenitor cell function in vivo and ex vivo. The ability of both SIV and HIV Nef to cause this problem was dependent on the hematopoietic progenitor cells expressing the protein PPAR-gamma. Further, when PPAR-gamma agonists were administered to macaques they impaired hematopoietic progenitor cell function. Disruption of hematopoietic progenitor cell function by both PPAR-gamma agonists and SIV and HIV Nef was associated with downregulation of the signaling molecules STAT5A and STAT5B, indicating that Nef is likely to impair blood cell development by targeting a PPAR-gamma/STAT5 signaling pathway. The authors have therefore suggested that PPAR-gamma antagonists might be of benefit to both individuals infected with HIV and those with blood cell–deficiency disorders. As noted by the authors and, in an accompany commentary, Frank Kirchhoff and Guido Silvestri, these data also have implications for PPAR-gamma agonists, which are currently used to treat individuals with type 2 diabetes.