Alzheimer’s disease (AD) progressively inflicts impairment of synaptic functions with notable deposition of amyloid-β (Aβ) as senile plaques within the extracellular space of the brain. Accordingly, therapeutic directions for AD have focused on clearing Aβ plaques or preventing amyloidogenesis based on the amyloid cascade hypothesis. However, the emerging evidence suggests that Aβ 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 Aβ and current Aβ-directed therapies in clinical trials. Based on the evidence, we propose that novel therapeutics targeting Aβ should selectively target Aβ in neurotoxic forms such as oligomers while retaining monomeric Aβ in order to preserve the physiological functions of Aβ monomers.
|Number of pages||24|
|Publication status||Published - 2022 Apr 1|
Bibliographical noteFunding Information:
This research was supported by the Korea Health Technology R&D Project (Grant Number: HU21C0161) through the Korea Health Industry Development Institute (KHIDI) and Korea Dementia Research Center (KDRC), and Mid-Career Researcher Program (Grant Number: NRF-2021R1A2C2093916), and Basic Science Research Program (Grant Number: NRF-2018R1A6A1A03023718) through the National Research Foundation of Korea (NRF), funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea. This research was also supported by Yonsei Frontier Lab,Amyloid Solution, and POSCO Science Fellowship of POSCO TJ Park Foundation.
© Experimental Neurobiology 2022.
All Science Journal Classification (ASJC) codes
- Clinical Neurology
- Cellular and Molecular Neuroscience