A different perspective on the factors that cause Alzheimer’s disease? Will it help bring about successful treatments?
*Pannuzzo, M. (2021, May 29). Beta-amyloid pore linked to controlled calcium influx into the cell: A new paradigm for Alzheimer’s disease. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association. [PDF]
“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 (Aβ) 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 Aβ-mediated synaptic plasticity and Aβ trafficking is central for understanding AD pathogenesis and remains a perplexing relationship. The crossover between Aβ pathological and physiological roles is subtle and remains controversial. Based on existing literature, as a signaling molecule, Aβ 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 Aβ pores exert a protective function will unavoidably revolutionize the entire field of anti-amyloid drug development.
There are meaningful analogies between AD, autism, and Down syndrome (DS), reinforcing the notion of an Aβ-mediated physiological regulation of synaptic plasticity.
The results of this investigation suggest that the Aβ-pore might afford protection against neuronal injury by promoting Ca2+ [calcium] influx to supply the cell’s physiological demands in response to hyperexcitation.”
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