TAILIEUCHUNG - Báo cáo khoa học: Amyloid oligomers: formation and toxicity of Ab oligomers

Alzheimer’s disease (AD) is an age-related, progressive degenerative dis-order that is characterized by synapse and neuron loss in the brain and the accumulation of protein-containing deposits (referred to as ‘senile plaques’) and neurofibrillary tangles. Insoluble amyloid b-peptide (Ab) fibrillar aggregates found in extracellular plaques have long been thought to cause the neurodegenerative cascades of AD. | ễFEBS Journal MINIREVIEW Amyloid oligomers formation and toxicity of Ab oligomers Masafumi Sakono1 2 and Tamotsu Zako1 1 Bioengineering Laboratory RIKEN Institute Wako Saitama Japan 2 PRESTO Japan Science and Technology Agency Kawaguchi Saitama Japan Keywords Alzheimer s disease amyloid b formation and toxicity mechanism intracellularand extracellular oligomers soluble amyloid oligomers Correspondence T. Zako Bioengineering Laboratory RIKEN Institute 2-1 Hirosawa Wako Saitama 351-0198 Japan Fax 81 48 462 4658 Tel 81 48 467 9312 E-mail zako@ Received 4 September 2009 revised 11 December 2009 accepted 6 January 2010 doi Alzheimer s disease AD is an age-related progressive degenerative disorder that is characterized by synapse and neuron loss in the brain and the accumulation of protein-containing deposits referred to as senile plaques and neurofibrillary tangles. Insoluble amyloid b-peptide Ab fibrillar aggregates found in extracellular plaques have long been thought to cause the neurodegenerative cascades of AD. However accumulating evidence suggests that prefibrillar soluble Ab oligomers induce AD-related synaptic dysfunction. The size of Ab oligomers is distributed over a wide molecular weight range from 10 kDa to 100 kDa with structural polymorphism in Ab oligomers of similar sizes. Recent studies have demonstrated that Ab can accumulate in living cells as well as in extracellular spaces. This review summarizes current research on Ab oligomers focusing on their structures and toxicity mechanism. We also discuss possible formation mechanisms of intracellular and extracellular Ab oligomers. Introduction Alzheimer s disease AD is an age-related progressive degenerative disorder characterized by the loss of synapses and neurons from the brain and by the accumulation of extracellular protein-containing deposits referred to as senile plaques and neurofibrillary tangles 1 . Amyloid b-peptide Ab 39-43 amino acids in length is the

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