Protein Prenylation and Synaptic Plasticity: Implications for Alzheimer’s Disease

David A. Hottman, Ling Li

Research output: Contribution to journalReview articlepeer-review

31 Scopus citations

Abstract

Protein prenylation is an important lipid posttranslational modification of proteins. It includes protein farnesylation and geranylgeranylation, in which the 15-carbon farnesyl pyrophosphate or 20-carbon geranylgeranyl pyrophosphate is attached to the C-terminus of target proteins, catalyzed by farnesyl transferase or geranylgeranyl transferases, respectively. Protein prenylation facilitates the anchoring of proteins into the cell membrane and mediates protein–protein interactions. Among numerous proteins that undergo prenylation, small GTPases represent the largest group of prenylated proteins. Small GTPases are involved in regulating a plethora of cellular functions including synaptic plasticity. The prenylation status of small GTPases determines the subcellular locations and functions of the proteins. Dysregulation or dysfunction of small GTPases leads to the development of different types of disorders. Emerging evidence indicates that prenylated proteins, in particular small GTPases, may play important roles in the pathogenesis of Alzheimer’s disease. This review focuses on the prenylation of Ras and Rho subfamilies of small GTPases and its relation to synaptic plasticity and Alzheimer’s disease.

Original languageEnglish (US)
Pages (from-to)177-185
Number of pages9
JournalMolecular neurobiology
Volume50
Issue number1
DOIs
StatePublished - Oct 2 2014

Bibliographical note

Funding Information:
Acknowledgments This work was supported in part by grants from the National Institutes of Health (AG031846), the Alzheimer’s Association (IIRG-09-131791), the BrightFocus Foundation (formerly American Health Assistance Foundation) (A2010328), the Alzheimer’s Drug Discovery Foundation, and the Academic Health Center of the University of Minnesota.

Keywords

  • Alzheimer’s disease
  • Farnesylation
  • Geranylgeranylation
  • Protein prenylation
  • Small GTPases
  • Synaptic plasticity

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