Structure-oriented review of 14-3-3 protein isoforms in geriatric neuroscience


  • This article was awarded the Novartis Prize by the Japan Geriatric Society.

Dr Takahiko Umahara MD PhD, Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku Shinjuku-ku, Tokyo 160-0023, Japan. Email:


This review focuses on the possible relevance of 14-3-3 proteins in geriatric neuroscience. 14-3-3 proteins are mainly localized in the synapses and neuronal cytoplasm. These proteins regulate intracellular signal cascades for differentiation, development, growth, apoptosis and survival. Seven isoforms have so far been identified in mammals. The binding motifs and potential functions of 14-3-3 proteins are now recognized to have a wide range of functional relevance. First, we provide a brief summary of the molecular structure and multiple functions of 14-3-3 proteins. Second, we review the involvement of 14-3-3 proteins in common diseases of geriatric neurology, such as Alzheimer's disease and tauopathies, Parkinson's disease and α-synucleinopathies, Huntington's disease and polyglutamine diseases, Creutzfeldt–Jakob disease and prion diseases, cerebral infarction, and atherosclerosis. Finally, we discuss the immunohistochemical localization of 14-3-3 proteins and its isoforms during the postnatal development of rat brains as a basis for understanding adult neurogenesis. The elucidation of the isoform-dependent functions of 14-3-3 proteins with regard to brain development might be promising for the future development of novel therapeutic interventions for common diseases of geriatric neurology. Geriatr Gerontol Int 2012; ••: ••–••.