Role of protein kinase A in regulating mitochondrial function and neuronal development: implications to neurodegenerative diseases

In neurons, enhanced protein kinase A (PKA) signaling elevates synaptic plasticity, promotes neuronal development, and increases dopamine synthesis. By contrast, a decline in PKA signaling contributes to the etiology of several brain degenerative diseases, including Alzheimer's disease and Parkinson's disease, suggesting that PKA predominantly plays a neuroprotective role. A-kinase anchoring proteins (AKAPs) are large multidomain scaffold proteins that target PKA and other signaling molecules to distinct subcellular sites to strategically localize PKA signaling at dendrites, dendritic spines, cytosol, and axons. PKA can be recruited to the outer mitochondrial membrane by associating with three different AKAPs to regulate mitochondrial dynamics, structure, mitochondrial respiration, trafficking, dendrite morphology, and neuronal survival. In this review, we survey the myriad of essential neuronal functions modulated by PKA but place a special emphasis on mitochondrially localized PKA. Finally, we offer an updated overview of how loss of PKA signaling contributes to the etiology of several brain degenerative diseases.