G proteins, p60TRP, and neurodegenerative diseases.
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.
Department of Biomedical Engineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Republic of Korea. klaus@hanyang.ac.kr
Klaus
K
Heese
D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D004705:Endocytosis / Q000235:genetics; D044127:Epigenesis, Genetic; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D019204:GTP-Binding Proteins