Bassoon, Presynaptic Scaffolding Protein: Narrative Review in Health and Disease

Abstract

The release of synaptic vesicles (SVs) at the synaptic junction is a complex process involving various specialized proteins that work in unison. Among these, Bassoon has emerged as a significant protein, particularly noted for its association with various neurological and aging-related diseases. Due to its structural and functional roles, Bassoon has become a focus of recent research, especially in understanding its implications in neurodegenerative and psychiatric disorders.

In this narrative review, we explore Bassoon's structure, function, and its role across a spectrum of neurological disorders. Neurotransmission is a tightly regulated process that relies on specialized structures within the presynaptic terminal, such as the presynaptic active zone (AZ), to precisely control SV release in response to incoming signals. The AZ comprises a complex network of large, multidomain proteins, with Bassoon playing a crucial role in this arrangement. Bassoon facilitates the tethering and reloading of SVs, ensuring responsiveness to high-frequency signals, while also maintaining proteostasis at the presynapse. This involves orchestrating the localization of proteins essential for neuronal development and plasticity.

Bassoon's large size and unique structural features enable it to interact with and regulate the function of multiple proteins, making it integral to presynaptic functioning. Variants in the Bassoon gene have been linked to a variety of neurodegenerative and psychiatric conditions, including Progressive Supranuclear Palsy, multiple system atrophy (MSA), epilepsy, schizophrenia, bipolar disorder, and Parkinson's disease. This review delves into Bassoon's pivotal role in preserving presynaptic integrity and how disruptions in its functions may contribute to these disorders.