Mitochondrial DNA damage in a mouse model of Alzheimer%26apos;s disease decreases amyloid beta plaque formation

作者：Pinto Milena; Pickrell Alicia M; Fukui Hirokazu; Moraes Carlos T^*

来源：Neurobiology of Aging, 2013, 34(10): 2399-2407.

DOI：10.1016/j.neurobiolaging.2013.04.014

• mtDNA damage
• Alzheimer
• Plaque formation
• APP cleavage
• ROS

Mitochondrial DNA (mtDNA) damage and the generation of reactive oxygen species have been associated with and implicated in the development and progression of Alzheimer%26apos;s disease. To study how mtDNA damage affects reactive oxygen species and amyloid beta (A beta) pathology in vivo, we generated an Alzheimer%26apos;s disease mouse model expressing an inducible mitochondrial-targeted endonuclease (Mito-PstI) in the central nervous system. Mito-PstI cleaves mtDNA causing mostly an mtDNA depletion, which leads to a partial oxidative phosphorylation defect when expressed during a short period in adulthood. We found that a mild mitochondrial dysfunction in adult neurons did not exacerbate Ab accumulation and decreased plaque pathology. Mito-PstI expression altered the cleavage pathway of amyloid precursor protein without increasing oxidative stress in the brain. These data suggest that mtDNA damage is not a primary cause of Ab accumulation.

• 出版日期2013-10