Fig. 2. Overall workflow of mass spectrometry (MS)-based peptidomics. Adopted from Schrader et al. EuPA Open Proteom 2014;3:171-182, according to Creative Commons License [33]. Peptidomics focuses on analyzing endogenous peptides that are present in biological samples, including brain tissue. In contrast to bottom-up proteomics studies that involve proteolytic digestion, it is important to minimize the activity of proteases that may be present in the samples via heat or microwave irradiation prior to peptide extraction in the peptidomics experiments. While the extracted peptides can be analyzed directly by matrix-assisted laser desorption/ionization (MALDI)-MS, they are often separated by reversed-phase chromatography or capillary electrophoresis in order to reduce sample complexity. Then, the peptides are analyzed by MS in order to obtain amino acid sequence information of the peptides without a priori knowledge. RP-HPLC, reverse phase-high performance liquid chromatography; LC-ESI-MS, liquid chromatography electrospray ionization mass spectrometry.