G proteins, p60TRP, and neurodegenerative diseases

Mol Neurobiol. 2013 Jun;47(3):1103-11. doi: 10.1007/s12035-013-8410-1. Epub 2013 Jan 24.


Alzheimer's disease (AD) is a complex brain disorder of the limbic system and association cortices. The disease is characterized by the production and deposition of the amyloid β-peptide (Aβ) in the brain, and the neuropathological mechanisms involved must be deciphered to gain further insights into the fundamental aspects of the protein biology responsible for the development and progression of this disease. Aβ is generated by the intramembranous cleavage of the β-amyloid precursor protein, which is mediated by the proteases β- and γ-secretase. Accumulating evidence suggests the importance of the coupling of this cleavage mechanism to G protein signaling. Heterotrimeric G proteins play pivotal roles as molecular switches in signal transduction pathways mediated by G protein-coupled receptors (GPCRs). Extracellular stimuli activate these receptors, which in turn catalyze guanosine triphosphate-guanosine diphosphate exchange on the G protein α-subunit. The activation-deactivation cycles of G proteins underlie their crucial functions as molecular switches for a vast array of biological responses. The novel transcription regulator protein p60 transcription regulator protein and its related GPCR signaling pathways have recently been described as potential targets for the development of alternative strategies for inhibiting the early signaling mechanisms involved in neurodegenerative diseases such as AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Endocytosis / genetics
  • Epigenesis, Genetic
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / physiopathology
  • Neuronal Plasticity / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • GTP-Binding Proteins