Protofibrillien

Protofibrillien are intermediate aggregates that form during the assembly of amyloid fibrils, the highly ordered beta‑sheet rich structures associated with various diseases. They are typically transient, soluble complexes composed of a few monomeric units that have begun to align but have not yet adopted the full fibrillar conformation. The term derives from the German for “proto‑fibril,” reflecting their role as precursors to mature fibrils.

In vitro studies show that protofibrillien appear early in the aggregation pathway of proteins such as amyloid‑beta, alpha‑synuclein, and huntingtin. They accumulate under conditions of protein concentration, pH, and temperature that favor partial folding and oligomerization. Spectroscopic techniques—including electron microscopy, atomic force microscopy, and circular dichroism—have revealed their size distribution (generally 10–100 nanometers) and beta‑sheet content, which is less ordered than in mature fibrils.

These species are of particular interest because they often exhibit cytotoxic activity in cell culture and animal models, suggesting a mechanistic link between early aggregation and cellular pathology. Consequently, many therapeutic strategies aim to stabilize protofibrillien either by preventing their formation or by promoting their conversion into less toxic, mature fibrils.

Research continues to refine the structural definition of protofibrillien, distinguishing them from both discrete oligomers and fully formed fibrils. The consensus view recognizes them as a distinct, dynamic stage in protein aggregation with significant implications for both basic science and clinical intervention.