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Pharmaceuticals 2010, 3(6), 1936-1948; doi:10.3390/ph3061936
Review

Unlocking the Door to Neuronal Woes in Alzheimer’s Disease: Aβ and Mitochondrial Permeability Transition Pore

1 and 1,2,3,*
Received: 10 May 2010; in revised form: 10 June 2010 / Accepted: 14 June 2010 / Published: 14 June 2010
(This article belongs to the Special Issue Mitochondrial Drugs for Neurodegenerative Diseases)
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Abstract: Mitochondrial dysfunction occurs early in the progression of Alzheimer’s disease. Amyloid-β peptide has deleterious effects on mitochondrial function and contributes to energy failure, respiratory chain impairment, neuronal apoptosis, and generation of reactive oxygen species in Alzheimer’s disease. The mechanisms underlying amyloid-β induced mitochondrial stress remain unclear. Emerging evidence indicates that mitochondrial permeability transition pore is important for maintenance of mitochondrial and neuronal function in aging and neurodegenerative disease. Cyclophilin D (Cyp D) plays a central role in opening mitochondrial permeability transition pores, ultimately leading to cell death. Interaction of amyloid-β with cyclophilin D triggers or enhances the formation of mitochondrial permeability transition pores, consequently exacerbating mitochondrial and neuronal dysfunction, as shown by decreased mitochondrial membrane potential, impaired mitochondrial respiration function, and increased oxidative stress and cytochrome c release. Blockade of cyclophilin D by genetic abrogation or pharmacologic inhibition protects mitochondria and neurons from amyloid-β induced toxicity, suggesting that cyclophilin D dependent mitochondrial transition pores are a therapeutic target for Alzheimer’s disease.
Keywords: amyloid beta; mitochondrial permeability transition; cyclophilin D; therapy amyloid beta; mitochondrial permeability transition; cyclophilin D; therapy
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Du, H.; ShiDu Yan, S. Unlocking the Door to Neuronal Woes in Alzheimer’s Disease: Aβ and Mitochondrial Permeability Transition Pore. Pharmaceuticals 2010, 3, 1936-1948.

AMA Style

Du H, ShiDu Yan S. Unlocking the Door to Neuronal Woes in Alzheimer’s Disease: Aβ and Mitochondrial Permeability Transition Pore. Pharmaceuticals. 2010; 3(6):1936-1948.

Chicago/Turabian Style

Du, Heng; ShiDu Yan, Shirley. 2010. "Unlocking the Door to Neuronal Woes in Alzheimer’s Disease: Aβ and Mitochondrial Permeability Transition Pore." Pharmaceuticals 3, no. 6: 1936-1948.


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