TY - JOUR
T1 - Targeting microRNA-485-3p blocks alzheimer’s disease progression
AU - Koh, Han Seok
AU - Lee, Sangjoon
AU - Lee, Hyo Jin
AU - Min, Jae-Woong
AU - Iwatsubo, Takeshi
AU - Teunissen, Charlotte E.
AU - Cho, Hyun-Jeong
AU - Ryu, Jin-Hyeob
N1 - Funding Information: This research was supported in part by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2017M3A9G2094069) and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C1671) and by grant-in-aid funds from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (19K16665 to S.L.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: Funding: This research was supported in part by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2017M3A9G2094069) and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C1671) and by grant-in-aid funds from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (19K16665 to S.L.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Alzheimer’s disease (AD) is a form of dementia characterized by progressive memory decline and cognitive dysfunction. With only one FDA-approved therapy, effective treatment strategies for AD are urgently needed. In this study, we found that microRNA-485-3p (miR-485-3p) was overexpressed in the brain tissues, cerebrospinal fluid, and plasma of patients with AD, and its antisense oligonucleotide (ASO) reduced Aβ plaque accumulation, tau pathology development, neuroinflammation, and cognitive decline in a transgenic mouse model of AD. Mechanistically, miR-485-3p ASO enhanced Aβ clearance via CD36-mediated phagocytosis of Aβ in vitro and in vivo. Furthermore, miR-485-3p ASO administration reduced apoptosis, thereby effectively decreasing truncated tau levels. Moreover, miR-485-3p ASO treatment reduced secretion of proinflammatory cytokines, including IL-1β and TNF-α, and eventually relieved cognitive impairment. Collectively, our findings suggest that miR-485-3p is a useful biomarker of the inflammatory pathophysiology of AD and that miR-485-3p ASO represents a potential therapeutic candidate for managing AD pathology and cognitive decline.
AB - Alzheimer’s disease (AD) is a form of dementia characterized by progressive memory decline and cognitive dysfunction. With only one FDA-approved therapy, effective treatment strategies for AD are urgently needed. In this study, we found that microRNA-485-3p (miR-485-3p) was overexpressed in the brain tissues, cerebrospinal fluid, and plasma of patients with AD, and its antisense oligonucleotide (ASO) reduced Aβ plaque accumulation, tau pathology development, neuroinflammation, and cognitive decline in a transgenic mouse model of AD. Mechanistically, miR-485-3p ASO enhanced Aβ clearance via CD36-mediated phagocytosis of Aβ in vitro and in vivo. Furthermore, miR-485-3p ASO administration reduced apoptosis, thereby effectively decreasing truncated tau levels. Moreover, miR-485-3p ASO treatment reduced secretion of proinflammatory cytokines, including IL-1β and TNF-α, and eventually relieved cognitive impairment. Collectively, our findings suggest that miR-485-3p is a useful biomarker of the inflammatory pathophysiology of AD and that miR-485-3p ASO represents a potential therapeutic candidate for managing AD pathology and cognitive decline.
KW - Alzheimer’s disease
KW - Antisense oligonucleotide
KW - Cognitive function
KW - IL-1β
KW - MiR-485-3p
KW - MicroRNA
KW - Neuroinflammation
KW - TNF-α
KW - Tau
KW - β-amyloid
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85120617658&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/34884940
UR - http://www.scopus.com/inward/record.url?scp=85120617658&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms222313136
DO - https://doi.org/10.3390/ijms222313136
M3 - Article
C2 - 34884940
SN - 1661-6596
VL - 22
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 23
M1 - 13136
ER -