Figure 2.

Mutations affecting MT polymerization and/or fibrillar aggregation. Pathogenetic mechanisms underlying tau mutations are depicted. Most of tau mutations reduce the protein ability to promote MT polymerization (A) and/or increase the propensity to aggregate into fibrils (B) (“Common pathological mechanisms”). However, a few tau mutations act in the opposite way, increasing MT polymerization (C) and/or decreasing the propensity to aggregate (D) (“Uncommon pathological mechanisms”). Alterations of MT dynamics, both as destabilization or over-stabilization, may anyway lead to cell degeneration. Oligomer toxicity (interaction with cell membrane, calcium uptake, mithocondrial dysfunction) is now widely confirmed; fibrillar aggregation, even if it might be considered as an attempt by the cell to sequester and neutralize oligomer toxicity, is however a structural and functional burden to cell.