Neuronal vesicular trafficking and release in age-related cognitive impairment

Aging is a common major risk factor for many neurological disorders resulting in cognitive impairment and neurodegeneration including Parkinson's and Alzheimer's diseases. Novel results from the fields of molecular neuroscience and aging research provide evidence for a link between decline of various cognitive, executive functions and changes in neuronal mechanisms of intracellular trafficking and regulated vesicle release processes in the aging nervous system. In this Perspective, we review these recent findings and formulate a hypothesis on how cargo delivery to the synapses and the release of neurotrophic factors may be involved in maintaining learning and memory capabilities during healthy aging and present examples on how defects of those disrupt normal cognition. We provide an overview of emerging new concepts and approaches that will significantly advance our understanding of the aging brain and pathophysiology of dementia. This knowledge will be instrumental in defining drug targets and designing novel therapeutic strategies.