Alzheimer鈥檚 Disease: A Heme鈥揂尾 Perspective

详细信息    查看全文

• 作者：Chandradeep Ghosh ; Manas Seal ; Soumya Mukherjee ; Somdatta Ghosh Dey
• 刊名：Accounts of Chemical Research
• 出版年：2015
• 出版时间：September 15, 2015
• 年：2015
• 卷：48
• 期：9
• 页码：2556-2564
• 全文大小：633K
• ISSN：1520-4898

文摘

Redox active iron is utilized in biology for various electron transfer and catalytic reactions essential for life, yet this same chemistry mediates the formation of partially reduced oxygen species (PROS). Oxidative stress derived from the iron accumulated in the amyloid plaques originating from amyloid 尾 (A尾) peptides and neurofibrillary tangles derived from hyperphosphorylated tau proteins has been implicated in the pathogenesis of Alzheimer鈥檚 disease (AD). Altered heme homeostasis leading to dysregulation of expression of heme proteins and heme deposits in the amyloid plaques are characteristic of the AD brain. However, the pathogenic significance of heme in neurodegeneration in AD has been unappreciated due to the lack of detailed understanding of the chemistry of the interaction of heme and A尾 peptides. As a result, the biochemistry and biophysics of heme complexes of A尾 peptides (heme鈥揂尾) remained largely unexplored.