Quantitative proteomic analysis of age-related subventricular zone proteins associated with neurodegenerative dise

Developers

Xianli Wang, Chuanming Dong, Lixin Sun, Jinfu Zhang, Jun Xu, etc.

Description of the technology

Aging is characterized by a progressive decline in the function of adult tissues, which can lead to neurodegenerative disorders. However, little is known about the correlation between protein changes in the subventricular zone and neurodegenerative diseases with age.

In this technology, these correlations were studied by proteomic analysis. Neural stem cells were derived from the subventricular zone on postnatal 7 d, 1 m, and 12 m-old mice. With age, neural stem cells exhibited increased senescence-associated beta-galactosidase (SA-β-gal) activity and decreased proliferation and pool size in the subventricular zone, and were associated with elevated levels of inflammatory chemokines and cytokines. Furthermore, quantitative proteomics and ingenuity pathway analysis were used to evaluate the significant age-related alterations in specific proteins and their functions. Functionally, these proteins were mainly associated with neurological disease, lipid metabolism, and small molecule biochemistry. Importantly, the downregulated expression patterns of these proteins are highly correlated with the loss of proteostasis and neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. For example, the proteasome subunit alpha type-1 (PSMA1), proteasome subunit alpha type-3 (PSMA3), PSMC2, PSMD11, and UCHL1 were decreased with age, which was consistent with the loss of proteostasis and neural stem cell senescence. On the other hand, TPI1, ALDH2, DPYSL2, and ApoE were decreased with age, consistent with the involvement in the neurodegeneration processes.

Taken together, these findings provided valuable insight into the cellular and molecular processes that underlie aging-associated declines in subventricular zone neurogenesis.

Practical application

This technology can be highly valuable for the early detection of differences in gene expression and the potential risk of neurological diseases. It can be beneficial in the investigation, prevention and early start of treatment of these diseases.

Laboratories

• East Hospital, Tongji University School of Medicine, Shanghai (China)
• Department of Anatomy, Nantong University, Nantong, Jiangsu (China)
• Department of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield (UK)
• Department of Urology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

Links

Publications

• Wang, X. et al. «Quantitative proteomic analysis of age-related subventricular zone proteins associated with neurodegenerative disease." 6 Scientific Reports, (2016): 37443.
• Dong, C. M. et al. «A stress-induced cellular aging model with postnatal neural stem cells." 5 Cell Death Dis, (201 $): e1116.