Fading memories in aging and neurodegeneration: Is p75 neurotrophin receptor a culprit?

Aging and age-related neurodegenerative diseases have become one of the major concerns in modern times as cognitive abilities tend to decline when we get older. It is well known that the main cause of this age-related cognitive deficit is due to aberrant changes in cellular, molecular circuitry and signaling pathways underlying synaptic plasticity and neuronal connections. The p75 neurotrophin receptor (p75) is one of the important mediators regulating the fate of the neurons in the nervous system. Its importance in neuronal apoptosis is well documented. However, the mechanisms involving the regulation of p75 in synaptic plasticity and cognitive function remain obscure, although cognitive impairment has been associated with a higher expression of p75 in neurons. In this review, we discuss the current understanding of how neurons are influenced by p75 function to maintain normal neuronal synaptic strength and connectivity, particularly to support learning and memory in the hippocampus. We then discuss the age-associated alterations in neurophysiological mechanisms of synaptic plasticity and cognitive function. Furthermore, we also describe current evidence that has begun to elucidate how p75 regulates synaptic changes in aging and age-related neurodegenerative diseases, focusing on the hippocampus. Elucidating the role that p75 signaling plays in regulating synaptic plasticity will contribute to a better understanding of cognitive processes and pathological conditions. This will in turn provide novel approaches to improve therapies for the treatment of neurological diseases in which p75 dysfunction has been demonstrated.