Beta-amyloid pore linked to controlled calcium influx into the cell: A new paradigm for Alzheimer's Disease

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.

Automated summary

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.