| Literature DB >> 17080199 |
Ina Tesseur1, Kun Zou, Luke Esposito, Frederique Bard, Elisabeth Berber, Judith Van Can, Amy H Lin, Leslie Crews, Patrick Tremblay, Paul Mathews, Lennart Mucke, Eliezer Masliah, Tony Wyss-Coray.
Abstract
Alzheimer's disease (AD) is characterized by progressive neurodegeneration and cerebral accumulation of the beta-amyloid peptide (Abeta), but it is unknown what makes neurons susceptible to degeneration. We report that the TGF-beta type II receptor (TbetaRII) is mainly expressed by neurons, and that TbetaRII levels are reduced in human AD brain and correlate with pathological hallmarks of the disease. Reducing neuronal TGF-beta signaling in mice resulted in age-dependent neurodegeneration and promoted Abeta accumulation and dendritic loss in a mouse model of AD. In cultured cells, reduced TGF-beta signaling caused neuronal degeneration and resulted in increased levels of secreted Abeta and beta-secretase-cleaved soluble amyloid precursor protein. These results show that reduced neuronal TGF-beta signaling increases age-dependent neurodegeneration and AD-like disease in vivo. Increasing neuronal TGF-beta signaling may thus reduce neurodegeneration and be beneficial in AD.Entities:
Mesh：
Substances：
Year: 2006 PMID： 17080199 PMCID： PMC1626127 DOI： 10.1172/JCI27341
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808