Brain-Derived Neurotrophic Factor Trafficking via the Regulated Secretory Pathway: Mechanisms and Disease...

Brain-derived neurotrophic factor (BDNF) plays an essential role in neuronal development and synaptic plasticity. BDNF's role in neuronal function is dependent on its trafficking through the regulated secretory pathway (RSP). This review provides a synthesis of the molecular mechanisms underlying anterograde BDNF trafficking with an emphasis on the role of sorting receptors (e.g., sortilin, carboxypeptidase E), motor proteins (e.g., kinesin), and scaffolding proteins (e.g., huntingtin, huntingtin-associated protein-1 1, dynactin). Despite major advances in elucidating the molecular players involved in BDNF trafficking, many regulators, such as adaptor proteins, ADP ribosylation factor GTPases, granins, and myosins, remain poorly characterized. However, given that impaired BDNF trafficking has been implicated in multiple neurodegenerative, neuropsychiatric, and neurodevelopmental disorders, understanding the trafficking of BDNF in full not only uncovers fundamental aspects of BDNF function but also reveals potential therapeutic targets for neurological disorders that are associated with impaired BDNF trafficking. This review summarizes current knowledge of anterograde BDNF trafficking from biosynthesis to regulated exocytosis and highlights its importance for neuronal function and human disease.