KMID : 0892920220310020065
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Experimental Neurobiology 2022 Volume.31 No. 2 p.65 ~ p.88
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Physiological Roles of Monomeric Amyloid-¥â and Implications for Alzheimer¡¯s Disease Therapeutics
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Jeong Hyo-Min
Shin Hee-Won Hong Seung-Pyo Kim Young-Soo
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Abstract
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Alzheimer¡¯s disease (AD) progressively inflicts impairment of synaptic functions with notable deposition of amyloid-¥â (A¥â) as senile plaques within the extracellular space of the brain. Accordingly, therapeutic directions for AD have focused on clearing A¥â plaques or preventing amyloidogenesis based on the amyloid cascade hypothesis. However, the emerging evidence suggests that A¥â serves biological roles, which include suppressing microbial infections, regulating synaptic plasticity, promoting recovery after brain injury, sealing leaks in the blood-brain barrier, and possibly inhibiting the proliferation of cancer cells. More importantly, these functions were found in in vitro and in vivo investigations in a hormetic manner, that is to be neuroprotective at low concentrations and pathological at high concentrations. We herein summarize the physiological roles of monomeric A¥â and current A¥â-directed therapies in clinical trials. Based on the evidence, we propose that novel therapeutics targeting A¥â should selectively target A¥â in neurotoxic forms such as oligomers while retaining monomeric A¥â in order to preserve the physiological functions of A¥â monomers.
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KEYWORD
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Alzheimer¡¯s disease, Amyloid beta-peptides, Amyloidosis, Neurodegenerative diseases, Therapeutics
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