Beta-amyloid peptide promotes neurons differentiation and survival

• Main Authors: Pei-Yi Wu, 吳沛翊
• Other Authors: Yu-Min Kuo
• Format: Others
• Language: en_US
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/98292469966782248481

碩士 === 國立成功大學 === 細胞生物及解剖學研究所 === 93 === 　　Alzheimer’s disease (AD) is the most common cause of dementia in aged humans. Two neuropathological lesions characterize the disease: intraneuronal neurofibrillary tangles, which are composed of the tau protein, and extracellular accumulation of fibrillar amyloid β peptide (Aβ). The abnormal aggregation of Aβ peptide in brain is generally considered as one of the major causes in the pathogenesis of AD. However, recent studies demonstrated that Aβ plays an important role in the viability of neuron. Furthermore, it was suggested that Aβ could promote neuron progenitor cells differentiation. In this regard, I hypothesize that the physiological function of Aβ is conformation-dependent. That is when A�� in certain aggregated forms, it may promote neuron survival and/or differentiation, while in certain more aggregated forms, it transforms into neurotoxic identity. To obtain different aggregated forms, Aβ was dissolved in 2% NH4OH, neutralized to pH7.4 by 1N HCl/5 mM Tris, and incubated at room temperature for 24 h. Various A�� aggregated sizes were then separated into >1000, 300-1000, 100-300, 30-100, and <30 kDa using membrane molecular sieving technique. My results indicated Aβ40 at 30-100 kDa possessing the ability to promote human neuroblastoma cell, SH-SY5Y, proliferation and differentiation, while the larger aggregates of Aβ induce the SH-SY5Y cell death. Such effects were also evident in the primary cortical neurons. These results suggest that Aβ peptide at the size of 30-100 kDa can promote neuron proliferation and induce neuronal progenitor cells differentiation. In vivo, the 30-100 kDa Aβ40 peptides could promote neurogenesis and enhance the short-term memory of mice. The physiological functions of Aβ�� require further clarification.