Morphological change by overexpression of D385A dominant negative presenilin 1 in human neuroblastoma SH-SY5Y cells.

Abstract

Presenilin 1 (PS1) is a multifunctional protein, and its mutations are highly related to familial Alzheimer's disease (AD). In this study, we examined the effects of PS1 overexpression on neuronal morphology using SH-SY5Y cells. Overexpression of dominant-negative D385A PS1 induced morphological change and impairment of neurite formation, while those of wild-type and pathogenic P117L mutant PS1 did not change cellular morphology compared with native cells. Moreover, filopodium-formation-related proteins were decreased only in cells overexpressing D385A PS1. Therefore, PS1 may be involved in neuritogenesis and morphological change in SH-SY5Y cells, and P117L mutation may linked to AD by different mechanisms.

• Authors: Daiju Tsuchiya, Yoshihisa Kitamura, Kazuyuki Takata, Takashi Taniguchi, Kengo Uemura, Hiroaki Miki, Tadaomi Takenawa, Shun Shimohama
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 102 Issue 3 Pg. 354-8 (Nov 2006) ISSN: 1347-8613 [Print] Japan
• PMID: 17099291 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Presenilin-1

Topics

• Brain Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Humans
• Immunoblotting
• Mutation (physiology)
• Neurites (physiology, ultrastructure)
• Neuroblastoma (genetics, metabolism, pathology)
• Presenilin-1 (biosynthesis, genetics)
• Pseudopodia (physiology, ultrastructure)