Protein Translation and Psychiatric Disorders

Although historically research has focused on transcription as the central governor of protein expression, protein translation is now increasingly being recognized as a major factor for determining protein levels within cells. The central nervous system relies on efficient updating of the protein landscape. Thus, coordinated regulation of mRNA localization, initiation, or termination of translation is essential for proper brain function. In particular, dendritic protein synthesis plays a key role in synaptic plasticity underlying learning and memory as well as cognitive processes. Increasing evidence suggests that impaired mRNA translation is a common feature found in numerous psychiatric disorders. In this review, we describe how malfunction of translation contributes to development of psychiatric diseases, including schizophrenia, major depression, bipolar disorder, and addiction.

Protein Synthesis and Synapse Specificity in Functional Plasticity

This chapter discusses the role of protein synthesis in the maintenance of long-term potentiation (LTP) and its associative properties, synaptic tagging and capture, which are cellular correlates of long-term memory. Starting from a brief overview of the early and late phases of LTP, the chapter discusses various existing models for synaptic activity-induced protein synthesis and its roles in late-LTP. The synaptic tagging and capture and cross-tagging theories are given emphasis, along with the elucidation of local dendritic protein synthesis and its significance in the maintenance of LTP. Inverse synaptic tagging, synaptic competition for plasticity-related proteins, and metaplasticity are also covered. The importance of the balance between proteasomal degradation and synthesis of plasticity-related proteins in persistent potentiation is briefly discussed. This chapter touches upon the physiological implications of epigenetic regulation in the control of neuronal functions and the molecular mechanisms within the neurons that translate epigenetic changes into long-lasting responses.