Microglial AGE-albumin is critical for neuronal death in Parkinson's disease: a possible implication for theranostics.
Advanced glycation end products (AGEs) are known to play an important role in the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD), by inducing protein aggregation and cross-link, formation of Lewy body, and neuronal death. In this study, we observed that AGE-albumin, the most abundant AGE product in the human PD brain, is synthesized in activated microglial cells and accumulates in the extracellular space. AGE-albumin synthesis in human-activated microglial cells is distinctly inhibited by ascorbic acid and cytochalasin treatment. Accumulated AGE-albumin upregulates the receptor to AGE, leading to apoptosis of human primary dopamine (DA) neurons. In animal experiments, we observed reduced DA neuronal cell death by treatment with soluble receptor to AGE. Our study provides evidence that activated microglial cells are one of the main contributors in AGE-albumin accumulation, deleterious to DA neurons in human and animal PD brains. Finally, activated microglial AGE-albumin could be used as a diagnostic and therapeutic biomarker with high sensitivity for neurodegenerative disorders, including PD.
Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea; Department of General Laboratory, National Cancer Center of Mongolia, Ulaanbaatar, Mongolia.
Enkhjargal
E
Bayarsaikhan
Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.
Delger
D
Bayarsaikhan
Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.
Jaesuk
J
Lee
Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea; Department of Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon, Republic of Korea.
Myeongjoo
M
Son
Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.
Seyeon
S
Oh
Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.
Jeongsik
J
Moon
Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.
Hye-Jeong
HJ
Park
Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.
Arivazhagan
A
Roshini
Department of Medicine, University of British Columbia, Vancouver, Canada.
Seung U
SU
Kim
Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Byoung-Joon
BJ
Song
Department of Emergency Medical Services, Eulji University, Seongnam-si, Gyeonggi-do, Republic of Korea.
Seung-Mook
SM
Jo
Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea; Department of Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon, Republic of Korea.
Kyunghee
K
Byun
Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea; Department of Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon, Republic of Korea.
Bonghee
B
Lee
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000473:pathology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D000068936:Theranostic Nanomedicine
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine
AGE-albumin; Parkinson’s disease; microglia; neuronal death; receptor of AGE; theragnostic