Antibody-bound β-amyloid precursor protein stimulates the production of tumor necrosis factor-α and monocyte chemoattractant protein-1 by cortical neurons

Neurobiology of Disease

Luc Mercken¹  Laurent Pradier¹  Nelly Frossard²  Jose-Luis González de Aguilar³  Corinne Mbebi³  Yves Larmet³  Luc Dupuis³  Violaine Sée³  Jean-Philippe Loeffler³ 

[1] Department of Neurodegenerative Disease Group, Aventis Pharma, 94400 Vitry-sur Seine, France;INSERM, U425, Faculté de Pharmacie, Université Louis Pasteur, 67000 Strasbourg, France;Laboratoire de Signalisations Moléculaires et Neurodégénérescence, INSERM, U692, Université Louis Pasteur, Faculté de Médecine, 11, rue Humann, 67085 Strasbourg cedex, France;

关键词: Alzheimer's disease;    β-amyloid precursor protein;    c-Jun N-terminal protein kinase;    Monocyte chemoattractant protein-1;    Neuronal death;    Tumor necrosis factor-α;   

DOI  :  

来源: DOAJ

【 摘 要 】

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the accumulation of extracellular depositions of fibrillar β-amyloid (Aβ), which is derived from the alternative processing of β-amyloid precursor protein (APP). Although APP is thought to function as a cell surface receptor, its mode of action still remains elusive. In this study, we found that the culture medium derived from cortical neurons treated with an anti-APP antibody triggers the death of naive neurons. Biochemical and immunocytochemical analyses revealed the presence, both in the conditioned medium and in neurons, of increased levels of tumor necrosis factor-α and monocyte chemoattractant protein-1. Furthermore, the expression of these proinflammatory mediators occurred through a c-Jun N-terminal protein kinase/c-Jun-dependent mechanism. Taken together, our findings provide evidence for a novel mechanism whereby neuronal APP in its full-length configuration induces neuronal death. Such a mechanism might be relevant to neuroinflammatory processes as those observed in AD.

【 授权许可】

Unknown