A team of researchers has shown that a molecule called Cyclophilin D (CypD) interacts with amyloid beta (AB) peptide, the main constituent of plaques in the brains of Alzheimer's patients, within the mitochondria.
The study involving a transgenic mouse model of Alzheimer's disease suggests that blocking CypD and development of surrounding mitochondrial targets may be viable therapeutic strategies for the prevention and treatment of Alzheimer's disease, reports Nature.
Study leader Shi Du Yan, professor of clinical pathology in the Department's of Pathology and Surgery and in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center, says that this work describes how this mitochondrial process may be linked to synaptic failure in Alzheimer's disease.
During the study, Dr. Yan and colleagues observed that the cortical mitochondria isolated from Alzheimer's disease mice lacking CypD were resistant to AB- and Ca2+-induced mitochondria swelling and permeability transition, increased calcium buffering capacity, and attenuate generation of mitochondrial ROS.
Also, they found that CypD-deficient neurons protect against AB- and oxidative stress-induced cell death.
Importantly, they researchers found that deficiency of CycD greatly improved the learning, memory, and synaptic function of an Alzheimer's disease mouse model and alleviated AB-mediated reduction of long-term potentiation (LTP).
Thus, the CypD/AB-mediated mitochondrial permeability transition pore directly links to the cellular and synaptic perturbation relevant to the pathogenesis of Alzheimer's disease.
The study is published in the Sept. 21 on-line edition of Nature Medicine.