Using mass spectrometry-based peptidomics to understand the brain and disorders such as Parkinson's disease and...

The numerous efforts invested in the identification of biomarkers for neurodegenerative and neuropsychiatric disorders, such as Parkinson's disease and schizophrenia, are justified because these disorders affect several million people worldwide. Although genetic implications and the role of the environment have been shown in the progression of those disorders, together with anatomical and neurochemical characteristics, an integrated view of the biochemical pathways involved in the pathophysiology of these disorders is still being unraveled. The use of proteomic methodologies, molecular mechanisms and potential biomarker candidates for the prognosis, diagnosis and treatment of brain disorders has been discussed. Similar methodologies can be applied for the large-scale identification of peptides to characterize the brain peptidome with the aim of closing the knowledge gaps that remain. Brain cells contain a large number of peptides that play pivotal roles in cell communication. Peptidome studies have recently identified more than 800 peptides in mouse brain extracts, with half of them derived from secretory pathways. For example, several of these peptides were identified as bioactive neuropeptides that activate G-coupled receptors. In addition, intracellular peptides derived from nuclear, cytosolic and mitochondrial proteins have been identified, including the hemopressins, which act with high selectivity for the cannabinoid receptor type 1. Considering the importance of peptides in cell signaling, the present review intends to discuss the recent findings of the peptidome field, focusing on Parkinson's disease and schizophrenia. New approaches to evaluate intracellular peptide signaling at the protein-protein interaction level and the future perspectives of peptides as intracellular modulators of signal transduction are explored.