Structural basis of bioenergetic protein complexes in Alzheimer's disease pathogenesis

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no cure where the underlying causes remain elusive. Mitochondrial dysfunction has become a prime suspect in AD pathogenesis since bioenergetic deficits precede the pathology. With advancing structural biology techniques at synchrotrons and cryo-electron microscopes, it is becoming possible to determine the structures of key proteins suspected to contribute to the initiation and propagation of AD, and investigate their interactions. In this review, we provide an overview of the recent developments concerning the structural aspects of mitochondrial protein complexes and their assembly factors involved the production of energy, in pursuit of therapies to halt or even reverse this disease in the early stages when mitochondria are most sensitive to amyloid toxicity.