한빛사논문
- 조회2,080
Abstract
Dong-Kyu Kimab, Hee-Sun Limb#, Ichiro Kawasakic, Yhong-Hee Shimc, Nishant N. Vaikathd, Omar M. A. El-Agnafe, He-Jin Leef & Seung-Jae Leea*
a Department of Biomedical Sciences and Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea
b Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea
c Department of Bioscience and Biotechnoloy and Institute of KU Biotechnology, Konkuk University, Seoul 05029, Korea
d Department of Biochemsitry, College of Medicine and Health Science, United Arab University, Al Ain, United Arab Emirates.
e Neurological Disorders Center, Qatar Biomedical Research Institute (QBRI), and College of Science and Engineering, Hamad Bin Khalifa University (HBKU), Education City, Qatar Foundation, P.O. Box 5825, Doha, Qatar
f Department of Anatomy, School of Medicine, Konkuk University, Seoul 05029, Korea
ABSTRACT
Aging is the major risk factor for neurodegenerative diseases that are also associated with impaired proteostasis, resulting in abnormal accumulation of protein aggregates. However, the role of aging in development and progression of disease remains elusive. Here, we used Caenorhabditis elegans models to show that aging-promoting genetic variations accelerated the rate of cell-to-cell transmission of SNCA/α-synuclein aggregates, hallmarks of Parkinson disease, and the progression of disease phenotypes, such as nerve degeneration, behavioral deficits, and reduced life span. Genetic and pharmacological anti-aging manipulations slowed the spread of aggregates and the associated phenotypes. Lysosomal degradation was significantly impaired in aging models, while anti-aging treatments reduced the impairment. Transgenic expression of hlh-30p::hlh-30, the master controller of lysosomal biogenesis, alleviated intercellular transmission of aggregates in the aging model. Our results demonstrate that the rate of aging closely correlates with the rate of aggregate propagation and that general anti-aging treatments can slow aggregate propagation and associated disease progression by restoring lysosomal function.
Keywords : aggregate propagation, aging, bimolecular fluorescence complementation, C. elegans, lysosome, Parkinson disease, SNCA/α-synuclein
논문정보
- Research article
- 2016년 08월 (BRIC 등록일 2016-08-12)
- 국내(교신)+국외 연구진
- 의약학 > 신경의학
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