Mitovesicles: a novel approach to understand and tackle neurodegeneration in Alzheimer ́s disease

Recent evidence suggests that mitochondria, which are dynamic and signaling organelles that supply energy in form of ATP, can be transferred between neuronal cells in specialized extracellular vesicles – named mitovesicles.

This mechanism is believed to support exogenous replacement of damaged mitochondria, offering an interesting therapeutic strategy.

Although the relevance of this transfer in neurodegeneration is largely unexplored, our preliminary data indicate that mitochondrial transfer is impaired in Alzheimer´s disease (AD).

AD is a progressive neurodegenerative disorder characterized by cognitive and functional decline for which no efficient disease-modifying drugs exist.

I hypothesize that alterations on mitochondrial network and dynamics in AD can lead to faulty packaging of mitovesicles, and consequently generate dysfunctional mitovesicles unable to produce ATP.

Therefore, in this project I propose to combine various experimental approaches to study mitovesicles formation, their proteomic and bioenergetic profile, and consequent transfer from astrocytes to neurons in AD models.

Additionally, I aim to identify and validate novel players directing functional mitovesicles formation and test their neuroprotective potential.

Overall, this project can bring the field of neuron-astrocyte metabolic crosstalk forward, greatly contributing to the understanding of cellular mechanisms influencing neurodegeneration and potentiate extracellular vesicles-based therapies.