Developmental regulation of presenilin-1 processing in the brain suggests a role in neuronal differentiation.

The Journal of Biological Chemistry
H HartmannB A Yankner

Abstract

Most cases of early-onset familial Alzheimer's disease are caused by mutations in the presenilin genes. Presenilin-1 (PS1) is subject to proteolytic cleavage resulting in the accumulation of N- and C-terminal fragments. In this report, we show that the proteolytic cleavage of PS1 is developmentally regulated in the brain. Low levels of full-length PS1 and higher levels of 30-kDa N-terminal and 20-kDa C-terminal fragments are identified at all developmental stages in the rat brain. However, in the adult brain, additional 36-kDa N-terminal and 14-kDa C-terminal fragments appear and become major PS1 species. Alternative N-terminal PS1 fragments also appear in the adult human brain, but are more heterogenous than in the rat brain. The alternative PS1 fragments are not detected at significant levels in rat or human peripheral tissues that express PS1. The alternative cleavage of PS1 is also detected in primary cultures of rat hippocampal neurons, but not in astrocytes, and is induced by neuronal differentiation. Furthermore, alternative PS1 cleavage is detected in rat PC12 cells and human neuroblastoma SH-SY5Y cells following induction of neuronal differentiation. These results suggest that an alternative pathway of PS1 proteolytic ...Continue Reading

References

Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·A Lorenzo, B A Yankner
Mar 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J BusciglioB A Yankner
Mar 15, 1996·Neuroscience Letters·H TakahashiK Imahori
Nov 1, 1996·Neuron·X Li, I Greenwald
Nov 1, 1996·Neuron·A DoanS S Sisodia
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·D LevitanI Greenwald
Mar 1, 1997·Neurobiology of Aging·K BaumannM Staufenbiel

❮ Previous
Next ❯

Citations

Oct 31, 2002·Human Psychopharmacology·Kurt Heininger
May 29, 1998·Brain Research. Molecular Brain Research·K R PennypackerM Hutton
Dec 15, 2000·Progress in Neurobiology·M F Mehler, S Gokhan
Apr 13, 2001·Neuroscience·B KostyszynE Sundström
May 7, 1999·Brain Research Bulletin·B S Shastry, F J Giblin
Jun 18, 1999·Brain Research Bulletin·K R PennypackerP R Sanberg
Feb 7, 1998·Current Opinion in Neurobiology·T W Kim, R E Tanzi
Nov 26, 2002·European Journal of Biochemistry·Martine Pastorcic, Hriday K Das
May 2, 2003·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Hiromi KeinoAtsuyoshi Shimada
Apr 16, 1998·The American Journal of the Medical Sciences·B S Shastry
Jul 31, 1998·Reviews in the Neurosciences·P L McGeerE G McGeer
Feb 12, 1998·Proceedings of the National Academy of Sciences of the United States of America·N N DewjiS J Singer
Sep 25, 2007·Progress in Neurobiology·Meng LiYan Zhang
Aug 15, 1997·The Journal of Biological Chemistry·H LoetscherH Jacobsen
Feb 7, 2001·Journal of Neurochemistry·S E CountsA I Levey
Dec 19, 2018·Frontiers in Molecular Neuroscience·Rocío NaranjoJosé R Naranjo
Jul 28, 2004·Biochemistry·Patrick C FraeringMichael S Wolfe

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Related Papers

The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society
P J McMillanD M Dorsa
Toxicology in Vitro : an International Journal Published in Association with BIBRA
C LindbladC J Fowler
© 2021 Meta ULC. All rights reserved