Revised neurofibril formation hypothesis

neuroscience19 Protein fibril formation is the coomon outcome in many neurodegenerative diseases. Before aggregating, single proteins misfold into anti-parallel or criss-crossed weave patterns. The misfolded proteins then begin to aggregate through intermediate form, ultimately growing into large stringy tangles called "fibrils". By this point, the aggregation has become lethal to the cells.
The scientists focused on the protein ataxin-3. When it mutates, ataxin-3 begins to aggregate and form fibrils with devastating consequences on motor control and coordination. This neurodegenerative disease is known as spinocerebellar ataxia.
Scientists showed that ataxin-3 misfold after it aggregates, not before as would be expected by current views on aggregation. In fact, the aggregation of ataxin-3 seems to begin with the individual protein, and then moves onto the formation of intermediate aggregation forms with the original protein structure rather than a misfolded one.