1.“Extracellular α-synuclein-a novel and crucial factor in Lewy body diseases.”, Lee HJ1, Bae EJ2, Lee SJ2., Nat Rev Neurol., 2014.2; 10(2):92-8. (SCI, IF: 15.518)
Misfolding and intracellular aggregation of α-synuclein are thought to be crucial factors in the pathogenesis of Lewy body diseases (LBDs), such as Parkinson disease. However, the pathogenic modifications of this protein and the mechanisms underlying its activity have not been fully characterized. Recent studies suggest that small amounts of α-synuclein are released from neuronal cells by unconventional exocytosis, and that this extracellular α-synuclein contributes to the major pathological features of LBD, such as neurodegeneration, progressive spreading of α-synuclein pathology, and neuroinflammation. In this article, we review a rapidly growing body of literature on possible mechanisms by which extracellular α-synuclein contributes to LBD pathology, and discuss therapeutic approaches to target this form of α-synuclein to halt disease progression.
2.“Exosomal Proteins in the Aqueous Humor as Novel Biomarkers in Patients with Neovascular Age-related Macular Degeneration.”, Kang GY, Bang JY, Choi AJ, Yoon J, Lee WC, Choi S, Yoon S, Kim HC, Baek JH, Park HS, Lim HJ, Chung H., J Proteome Res., 2014.2.7; 13(2):581-95. (SCI, IF: 5.056)
Age-related macular degeneration (AMD) describes the progressive degeneration of the retinal pigment epithelium (RPE), retina, and choriocapillaris and is the leading cause of blindness in people over 50. The molecular mechanisms underlying this multifactorial disease remain largely unknown. To uncover novel secretory biomarkers related to the pathogenesis of AMD, we adopted an integrated approach to compare the proteins identified in the conditioned medium (CM) of cultured RPE cells and the exosomes derived from CM and from the aqueous humor (AH) of AMD patients by LC-ESI-MS/MS. Finally, LC-MRM was performed on the AH from patients and controls, which revealed that cathepsin D, cytokeratin 8, and four other proteins increased in the AH of AMD patients. The present study has identified potential biomarkers and therapeutic targets for AMD treatment, such as proteins related to the autophagy-lysosomal pathway and epithelial-mesenchymal transition, and demonstrated a novel and effective approach to identifying AMD-associated proteins that might be secreted by RPE in vivo in the form of exosomes. The proteomics-based characterization of this multifactorial disease could help to match a particular marker to particular target-based therapy in AMD patients with various phenotypes.
3.“Suppression of autophagic activation in the mouse uterus by estrogen and progesterone.”, Choi S, Shin H, Song H, Lim HJ., J Endocrinol., 2014.1.17 (SCI, IF: 4.058)
Autophagy is a major cellular catabolic pathway tightly associated with cell survival. The involvement of autophagy in the prolonged survival of blastocysts in the uterus is well established, and it was assumed that ovarian steroid hormones - progesterone and estrogens - have important roles in the regulation of autophagy. However, information is scarce regarding whether these hormones regulate autophagy in certain hormone-responsive cellular systems. In this study, we investigated the effects of estrogen and progesterone on autophagic response in the uteri of pregnant mice and in ovariectomized (OVX) mice treated with hormones. During pregnancy, autophagic response is high on days 1 and 2 when the uterus shows an inflammatory response to mating, but it subsides around the time of implantation. Dexamethasone treatment to day 1 pregnant mice reduced autophagy in the uterus. In OVX mouse uteri, estrogen or progesterone reduces autophagic response within 6 h. Glycogen content in OVX uteri was increased by 3-methyladenine treatment, suggesting that autophagy is involved in glycogen breakdown in the hormone-deprived uterus. Classical nuclear receptor antagonists, ICI 182780 or mifepristone, lead to recovery of the autophagic response in OVX uteri. Suppression of autophagy by E2 is inversely correlated with accumulation of phospho-mTOR, and rapamycin treatment is moderately effective in upregulating autophagic response in OVX mouse uteri. Collectively, this study establishes that the uterine autophagy is induced in hormone-derived environment and is suppressed by hormone treatment. Uterine autophagy may have multiple functions, as a responsive mechanism to acute inflammation and as an energy provider by breaking down glycogen under hormone deprivation.