Neuroproteomics and its applications in research on nicotine and other drugs of abuse

Abstract

The rapidly growing field of neuroproteomics is able to track changes in protein expression and protein modifications underlying various physiological conditions, including the neural diseases related to drug addiction. Thus, it presents great promise in characterizing protein function, biochemical pathways, and networks to understand the mechanisms underlying drug dependence. In this article, we first provide an overview of proteomics technologies and bioinformatics tools available to analyze proteomics data. Then we summarize the recent applications of proteomics to profile the protein expression pattern in animal or human brain tissues after the administration of nicotine, alcohol, amphetamine, butorphanol, cocaine, and morphine. By comparing the protein expression profiles in response to chronic nicotine exposure with those appearing in response to treatment with other drugs of abuse, we identified three biological processes that appears to be regulated by multiple drugs of abuse: energy metabolism, oxidative stress response, and protein degradation and modification. Such similarity indicates that despite the obvious differences among their chemical properties and the receptors with which they interact, different substances of abuse may cause some similar changes in cellular activities and biological processes in neurons.

Neurobiological Signatures of Alcohol Dependence Revealed by Protein Profiling

“…Moreover, brain imaging studies in human alcoholics showed a marked reduction in whole brain glucose metabolism and modified brain resource allocation [46], [47]. Neurons adjust their intra- and extra-cellular environment in the presence of alcohol, and a disturbance of energy-generation pathways with related mitochondrial dysfunction could have profound consequences, including generation of reactive oxygen-nitrogen species [45]. Our results provide further support for the role of energy-related changes in two different alcoholic stages.…”

“…Several proteins identified from the studies above and our current work are involved in basal energy metabolism (e.g., creatine kinase, enolase, malate dehydrogenase, phosphoglycerate mutase 1, pyruvate kinase) [29]–[31]. Proteins involved in energy metabolism are regulated by many drugs of abuse as shown by neuroproteomic approaches [45]. Moreover, brain imaging studies in human alcoholics showed a marked reduction in whole brain glucose metabolism and modified brain resource allocation [46], [47].…”

“…Alcohol-stimulated induction of heat shock proteins (HSPs) may be part of a protective response against oxidative stress [48]. HSPs are also regulated by several other drugs of abuse at both the mRNA and protein levels [45]. Alcohol can activate the heat shock pathway through the up-regulation of HSF1-dependent genes, Hsp70 and Hsp90, in cultured neurons and in mouse cerebral cortex [49].…”

“…Ethanol and heat shock response can also increase gene expression of Syt1 , Snap25 and Vamp2 , members of the SNARE complex that is in turn associated with the BK channel and dynamin-1 [40]. These changes could also represent a counter-regulatory action against the potentially toxic cellular effects of alcohol, rather than a general stress-like situation following its abuse [45].…”

Changes in salivary proteome before and after cigarette smoking in smokers compared to sham smoking in non-smokers: A pilot study

“…This response has been attributed to the nicotine in tobacco smoke 8 . In the drug dependence field, proteomics has been proposed to identify protein patterns that underlie psychological and neurological mechanisms 9 . A study demonstrated rapid effects of stress-induced HPA activation in rats, following only a 15-minute physical stressor 10 .…”