A number of unique challenges are inherent to the study of neuropeptides (NPs), both in determining their molecular
structure and their function. Traditional studies follow a model in which novel NPs are discovered and identified,
then investigated for function. These studies frequently use biochemical techniques that can be imprecise and cumbersome.
Mass spectrometry (MS)-based tools are becoming important not only in precisely determining the identity of a NP
or quantifying a compound with a known sequence, but also in studies where identity and putative function can be determined
simultaneously. Tools based on MS and tandem MS (MS/MS) have been developed, both with isotope labeling
strategies and label-free methods, that allow accurate quantitation of NP changes associated with behavior or physiological
manipulation, concurrent with identification of sequence. MS and MS/MS have also been implemented with sampling
methods that incorporate temporal or spatial information while determining functional role of a NP, such as microdialysis
(MD) and imaging mass spectrometry (IMS). These advances in MS and sampling techniques allow investigation of a particular
biological phenomenon to guide studies aimed to identify and characterize NPs. Permitting function to drive identification
of relevant compounds allows for a broader understanding of the molecular underpinnings of these events. The
NPs thus identified can then be validated with more conventional techniques, and successive iterations of identification
and function determination will provide rich information about these compounds. This function-driven discovery of NPs
using MS-based techniques is an important new approach for their study.
Keywords: Neuropeptides, mass spectrometry, identification, function, quantitation, microdialysis, imaging mass spectrometry.
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