Journal de la maladie d'Alzheimer et du parkinsonisme

Abstrait

Alzheimer’s Disease: Molecular Hallmarks and Yeast Models

Tatiana Goleva, Anton Rogov and Renata Zvyagilskaya

Alzheimer’s disease is a multifaceted, incurable neurologic disorder characterized by cognitive decline and degeneration of brain neurons. The main factors implicated in Alzheimer’s disease including accumulation of misfolded and aggregated proteins (hyperphosphorylated microtubule associated protein referred to as tau and amyloid Aβ), oxidative damage, inflammation, mitochondrial impairments and chronic energy imbalance, chronic endoplasmic reticulum stress, autophagy dysfunction, the abnormality and dysfunction of the mitochondrion-associated endoplasmic reticulum membrane serving as bridges between endoplasmic reticulum and mitochondria and regulating multiple functions such as Ca2+ transfer, energy exchange, lipid synthesis and transports and protein folding, genetic variation in lysosomal genes, metabolomic changes are shortly considered. A special emphasis was placed on mitochondrial fission (fragmentation) is a prominent early event preceding Alzheimer’s disease pathology in transgenic Aβ-animal models, as well as on marked decrease in extracellular amyloid deposition, prevention of the cognitive deficit development and improvement of synaptic parameters after inhibiting abnormalities in mitochondrial dynamics. The important role of the well-characterized Saccharomyces cerevisiae yeast as a valuable eukaryotic model organism in unraveling complex fundamental intracellular mechanisms underlying Alzheimer’s disease is highlighted. The benefits of applying a new model organism the yeast Yarrowia lipolytica, an obligate aerobe with the respiratory metabolism closely resembling that of mammalian cells, amenable to both classical and molecular genetic techniques, having a long history of use as a producer of heterological proteins, possessing an ability to change its morphology (from yeast-like to true mycelium) in response to environmental conditions as an useful alternative in deciphering a role of mitochondrial dynamics and distribution in an yeast model of Alzheimer’s disease are suggested.