The monomer state of beta-amyloid: where the Alzheimer's disease protein meets physiology.

M. L. Giuffrida, F. Caraci, P. De Bona, G. Pappalardo, F. Nicoletti, E. Rizzarelli, A. Copani

Research output: Contribution to journalArticle

Abstract

One hundred years of study have identified beta-Amyloid (A beta) as the most interesting feature of Alzheimer's disease (AD). Since the discovery of A beta as the principal component of amyloid plaques, the central challenge in AD research has been the understanding of A beta involvement in the neurodegenerative process of the disease. The ability of A beta to undergo conformational changes and subsequent aggregation has always been a limiting factor in finding out the activities of the peptide. Extensive research has been carried out to study the molecular mechanisms of amyloid self-assembly. The finding that soluble Abeta concentrations in the brain are correlated with the severity of AD, whereas fibrillar density is not /40,42/, has pointed attention toward the oligomeric forms of Abeta, which are generally considered the most toxic and, therefore, the most important species to be addressed. Despite great efforts in basic AD research, none of the currently available treatments is able to treat the devastating effects of the disease, leading to the consideration that there is more to reason than just A beta production and aggregation. Here we summarize the emerging evidence for the physiological functions of A beta, including our recent demonstration that A beta monomers are endowed with neuroprotective activity, and propose that A beta aggregation might contribute to AD pathology through a "loss-of-function" process. Finally, we discuss the current therapeutics targeting the cerebral load of A beta and possible new ones aimed at preserving the biological functions of A beta.

Original languageEnglish
Pages (from-to)83-93
Number of pages11
JournalReviews in the Neurosciences
Volume21
Issue number2
Publication statusPublished - 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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    Giuffrida, M. L., Caraci, F., De Bona, P., Pappalardo, G., Nicoletti, F., Rizzarelli, E., & Copani, A. (2010). The monomer state of beta-amyloid: where the Alzheimer's disease protein meets physiology. Reviews in the Neurosciences, 21(2), 83-93.