Cyclophilin D Deficiency Rescues Axonal Mitochondrial Transport in Alzheimer’s Neurons

• DOI: 10.1371/journal.pone.0054914
• Publication Date: 2013-01-31T22:28:28Z
• Authors: Lan Guo; Heng Du; Shiqiang Yan; Xiaoping Wu; Guy M. McKhann; John Xi Chen; Shirley ShiDu Yan
• Keywords: MPTP; Axoplasmic transport; DNAJA3

Normal axonal mitochondrial transport and function is essential for the maintenance of synaptic function. Abnormal motility dysfunction within axons are critical amyloid β (Aβ)-induced stress loss synapses relevant to pathogenesis Alzheimer's disease (AD). However, mechanisms controlling alterations in AD remain elusive. Here, we report an unexplored role cyclophilin D (CypD)-dependent permeability transition pore (mPTP) Aβ-impaired trafficking. Depletion CypD significantly protects dynamics from Aβ toxicity as shown by increased density distribution improved bidirectional mitochondria. Notably, blockade mPTP genetic deletion suppresses Aβ-mediated activation p38 mitogen-activated protein kinase signaling pathway, reverses abnormalities, improves function, attenuates synapse, suggesting a CypD-dependent Aβ-induced The potential protective effects lacking on abnormal axon calcium buffer capability, diminished reactive oxygen species (ROS), suppressing downstream signal transduction P38 activation. These findings provide new insights into trafficking degeneration environment enriched Aβ.