期刊
ALZHEIMERS & DEMENTIA
卷 18, 期 1, 页码 191-196出版社
WILEY
DOI: 10.1002/alz.12373
关键词
aging; Alzheimer's disease; beta-amyloid pore; calcium; cholesterol dyshomeostasis; endocytic trafficking; excitotoxicity; synaptic plasticity
资金
- European Union's Horizon 2020 research and innovation programme under the Marie Skodowska-Curie grant [754490-MINDED]
Despite continuous worldwide efforts, clinical trials for Alzheimer's disease (AD) therapeutics have not been successful. There is a new concept suggesting that the amyloid-beta (Aβ) peptide may modulate synaptic plasticity and protect against excitotoxicity, challenging the previous belief that it is a major contributor to AD pathogenesis. The relationship between Aβ-mediated synaptic plasticity and trafficking remains complex and controversial, indicating a need for further research.
Despite tremendous worldwide efforts, clinical trials assessing Alzheimer's disease (AD)-related therapeutics have been relentlessly unsuccessful. Hence, there is an urgent need to challenge old hypotheses with novel paradigms. An emerging concept is that the amyloid-beta (A beta) peptide, which was until recently deemed a major player in the cause of AD, may instead modulate synaptic plasticity and protect against excitotoxicity. The link between A beta-mediated synaptic plasticity and A beta trafficking is central for understanding AD pathogenesis and remains a perplexing relationship. The crossover between A beta pathological and physiological roles is subtle and remains controversial. Based on existing literature, as a signaling molecule, A beta is proposed to modulate its own turnover and synaptic plasticity through what is currently believed to be the cause of AD: the transient formation of pore-like oligomers. A change of perspective regarding how A beta pores exert a protective function will unavoidably revolutionize the entire field of anti-amyloid drug development.
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