Metal ion coordination in peptide fragments of neurotrophins: A crucial step for understanding the role and signaling of these proteins in the brain

Abstract Some metal ions of the d-block are necessary for the proper growth, functioning and maintenance of the central nervous system. In particular, copper and zinc ions have emerged as effective non-structural intracellular mediator of cell signaling. The high zinc and copper levels in the synaptic cleft are associated with the shaping of synaptic plasticity and, thus, with learning and memory formation processes. Recent findings identify neurotrophins (NTs) as potential targets of metal ions in the kinase signaling networks of neuronal tissues. Neurotrophins are a class of proteins crucial for the growth and preservation of the central nervous system as they preside over processes/functions like neuroplasticity, memory and learning. A deficit in the expression and activity of these proteins is associated to many neurodegenerative pathologies as Alzheimer and Parkinson’s diseases. Knowing the coordination chemistry of metal ions to NTs is an essential step to identify the basis of NTs/metal ions physiology in learning and memory formation as well as the factors that trigger memory impairment in neurodegeneration, NTs conformations, NTs chemical properties and their biological functions. Unfortunately, characterizing the metal ion coordination of the whole protein is hardly feasible if not impossible. Thus, the design and synthesis of peptides able to mimic the binding and functional sites of proteins may be a viable strategy to explore protein activity and conformational features, metal ion binding as well as to design new molecules for neurodegenerative disorders.