The regulatory role of cystatin C in autophagy and neurodegeneration

• Published in: Vavilov Journal of Genetics and Breeding
• Main Authors: T. A. Korolenko, A. B. Shintyapina, A. B. Pupyshev, A. A. Akopyan, G. S. Russkikh, M. A. Dikovskaya, V. A. Vavilin, E. L Zavjalov, M. A. Tikhonova, T. G. Amstislavskaya, Т. А. Короленко, А. Б. Шинтяпина, А. Б. Пупышев, А. А. Акопян, Г. С. Русских, М. А. Диковская, В. А. Вавилин, Е. Л. Завьялов, М. А. Тихонова, Т. Г. Амстиславская
• Other Authors: This work was supported partially by grant No. 16-04-01423-а from the Russian Foundation for Basic Research (Russia), to T.A.K., budget from the project No. 0538-2014-0009 of the Scientific Research Institute of Physiology and Basic Medicine (SRIPhBM) and a unique scientific resource “Biological collection – Genetic biomodels of neuro-psychiatric disorders” (No. 493387) at the SRIPhBM. The studies were implemented using the equipment of the Center for Genetic Resources of Laboratory Animals at ICG SB RAS, supported by the Ministry of Education and Science of Russia (unique identifier of the project: RFMEFI62117X0015).
• Format: Article in Journal/Newspaper
• Language: English
• Published: Institute of Cytology and Genetics of Siberian Branch of the RAS 2019
• Subjects: нейродегенерация; autophagy; neurodegeneration; аутофагия; Circumpolar Health
• Online Access: https://vavilov.elpub.ru/jour/article/view/2129; https://doi.org/10.18699/VJ19.507

Autophagy is a dynamic cellular process involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. It is particularly important in neurons, which do not have a proliferative option for cellular repair. Autophagy has been shown to be suppressed in the striatum of a transgenic mouse model of Parkinson’s disease. Cystatin C is one of the potent regulators of autophagy. Changes in the expression and secretion of cystatin C in the brain have been shown in amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s diseases, and in some animal models of neurodegeneration, thus proving a protective function of cystatin C. It has been suggested that cystatin C plays the primary role in amyloidogenesis and shows promise as a therapeutic agent for neurodegenerative diseases (Alzheimer’s and Parkinson’s diseases). Cystatin C colocalizes with the amyloid β-protein in the brain during Alzheimer’s disease. Controlled expression of a cystatin C peptide has been proposed as a new approach to therapy for Alzheimer’s disease. In Parkinson’s disease, serum cystatin C levels can predict disease severity and cognitive dysfunction, although the exact involvement of cystatin C remains unclear. The aim: to study the role of cystatin C in neurodegeneration and evaluate the results in relation to the mechanism of autophagy. In our study on humans, a higher concentration of cystatin C was noted in cerebrospinal fluid than in serum; much lower concentrations were observed in other biological fluids (intraocular fluid, bile, and sweat). In elderly persons (61–80 years old compared to practically healthy people at 40–60 years of age), we revealed increased cystatin C levels both in serum and intraocular fluid. In an experiment on C57Bl/6J mice, cystatin C concentration was significantly higher in brain tissue than in the liver and spleen: an indication of an important function of this cysteine protease inhibitor in the brain. Using a transgenic mouse model of Parkinson’s disease (5 months old), we ...