ALDH1A3 Segregated Expression and Nucleus-Associated Proteasomal Degradation Are Common Traits of Glioblastoma Stem Cells

Aldehyde dehydrogenase 1 isoforms A1 and A3 have been implicated as functional biomarkers associated with distinct molecular subtypes of glioblastoma and glioblastoma stem cells. However, the exact roles of these isoforms in different types of glioma cells remain unclear. The purpose of this study was to dissect the association of A1 or A3 isoforms with stem and non-stem glioblastoma cells. This study has undertaken a systematic characterization of A1 and A3 proteins in glioblastoma tissues and a panel of glioblastoma stem cells using immunocytochemical and immunofluorescence staining, Western blot and the subcellular fractionation methodology. Our main findings are (i) human GSCs express uniformly ALDH1A3 but not the ALDH1A1 isoform whereas non-stem glioma cells comparably express both isoforms; (ii) there is an abundance of ALDH1A3 peptides that prevail over the full-length form in glioblastoma stem cells but not in non-stem glioma cells; (iii) full-length ALDH1A3 and ALDH1A3 peptides are spatially segregated within the cell; and (vi) the abundance of full-length ALDH1A3 and ALDH1A3 peptides is sensitive to MG132-mediated proteasomal inhibition. Our study further supports the association of ALDH1A3 with glioblastoma stem cells and provide evidence for the regulation of ALDH1A3 activities at the level of protein turnover.

Normal development of the brain: a survey of joint structural-functional brain studies

Joint structural-functional (S-F) developmental studies present a novel approach to address the complex neuroscience questions on how the human brain works and how it matures. Joint S-F biomarkers have the inherent potential to model effectively the brain’s maturation, fill the information gap in temporal brain atlases, and demonstrate how the brain’s performance matures during the lifespan. This review presents the current state of knowledge on heterochronous and heterogeneous development of S-F links during the maturation period. The S-F relationship has been investigated in early-matured unimodal and prolonged-matured transmodal regions of the brain using a variety of structural and functional biomarkers and data acquisition modalities. Joint S-F unimodal studies have employed auditory and visual stimuli, while the main focus of joint S-F transmodal studies has been resting-state networks and working memory. However, non-significant associations between some structural and functional biomarkers and their maturation show that designing and developing effective S-F biomarkers is still a challenge in the field. Maturational characteristics of brain asymmetries have been poorly investigated by the joint S-F studies, and the results were inconsistent with previous non-joint ones. The inherent complexity of the brain performance can be modeled using multifactorial and nonlinear techniques as promising methods to simulate the impact of age on S-F relations considering their analysis challenges.