Figure 2.

Consequences of mitochondrial permeability transition in the AD brain: The role of canonical Wnt signaling in neuroprotection. Mitochondria are structured organelles, which in normal or healthy conditions (left panel) present a conserved structure of both the inner and outer mitochondrial membranes. This organization allows the formation of the mitochondrial cristae, which are important since therein resides the electron transport chain to support cellular respiration and neuronal viability. Under AD conditions (right panel), in the presence of Aβo, mitochondria undergo structural changes as a result of Aβ-induced mitochondrial membrane permeability. This phenomenon is triggered by the opening of the mitochondrial permeability transition pore (mPTP), which produces water and solute entry into the mitochondria, inducing increased mitochondrial volume and the loss of its structure, promotes mitochondrial membrane potential (mΔΨ) dissipation and the release of pro-apoptotic factors and calcium to the cytoplasm. These morphological changes that mitochondria undergo during membrane permeability are known as mitochondrial swelling, which finally generates the loss of mitochondrial function to activate neuronal cell death processes. Bottom panels show representative images obtained by electron microscopy of a healthy mitochondrion (left) with normal membrane and cristae structures and an AD mitochondrion (right) with disrupted membranes and cristae disorganization as a result of mitochondrial swelling induced by Aβo. Canonical Wnt signaling activation through the Wnt3a ligand prevents these morphological and structural changes, preserving the integrity and function of the mitochondria in the brain.