Impaired Balance of Mitochondrial Fission and Fusion in Alzheimer's Disease

• DOI: 10.1523/jneurosci.1357-09.2009
• Publication Date: 2009-07-15T17:28:25Z
• Authors: X. Wang; B. Su; H.-g. Lee; X. Li; G. Perry; M. A. Smith; X. Zhu
• Keywords: MFN2; FIS1; MFN1; DNAJA3

Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD) neurons. In this study, we explored the involvement an abnormal mitochondrial dynamics by investigating changes in expression fission and fusion proteins AD brain potential cause consequence these neuronal cells. We found that mitochondria were redistributed away from axons pyramidal neurons brain. Immunoblot analysis revealed levels DLP1 (also referred to as Drp1), OPA1, Mfn1, Mfn2 significantly reduced whereas Fis1 increased AD. Despite their differential effects on morphology, manipulations cells mimic expressional caused similar distribution pattern, such density was cell periphery M17 or process primary correlated with spine neurite. Interestingly, oligomeric amyloid-beta-derived diffusible ligands (ADDLs) fragmentation processes. More importantly, ADDL-induced synaptic change (i.e., loss dendritic postsynaptic protein 95 puncta) distribution. overexpression, likely through repopulation processes mitochondria, prevented loss, suggesting plays important role abnormalities. Based findings, suggest altered balance mechanism leading