Objectives: 

Drastic cognitive decline that occurs in different neuropathologies is largely related to functional changes in signal transduction cascades that modify neuronal responses. A large fraction of signaling proteins important for neuronal maintain are located in liquid-ordered domains, or lipid rafts, which are the preferential locations for these molecules due to the particular physico-chemical properties of these microdomains. In these microstructures, proteins interact with lipids and with other proteins, forming macromolecular complexes that may be considered specialized signaling platforms, or "signalosomes". These platforms may become activated upon association with a variety of stimuli, leading to the initiation of different signal transduction events that may promote neuronal survival against different injuries, such as Alzheimer's disease. Therefore, identification of crucial lipid markers and their interactions with target signaling proteins in lipid rafts are an important challenge to elucidate the mechanisms involved in this neuronal pathophysiology.

Materials: 

Neuronal cultured cells, lipid rafts from human frontal cortex

Results: 

In this order of ideas, we have identified in neuronal lipid rafts from, both, mouse and human, a protein complex formed by estrogen receptor (ER), caveolin-1 as a scaffolded protein, and a voltage-dependent anion channel (VDAC) which is involved in cell death induced by amyloid beta peptide. Our studies have demonstrated that the regulation of VDAC phosphorylation in the signalosome contributes to neuronal preservation against this toxicity.

Conclusions: 

Further work on these interactive microstructures will unveil important aspects of many neurological diseases.