Atomic force microscopy analysis of the Huntington protein nanofibril formation

The cytoskeletal architecture can be studied using different microscopic and biochemical techniques. Electron microscopy was instrumental in discovering the cytoskeletal architecture around the 1960s, which allowed obtaining structural information at a high-resolution level. However, the sample preparation procedure often limits this ability in biological samples. Several protocols have been developed over the years to optimize sample preparation. In one of the protocols known as rotary...

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...

Intermediate filaments are cytoskeletal proteins with higher tensile strength and flexibility than microfilaments and microtubules. Unlike the other two cytoskeletal proteins, intermediate filament formation lacks the enzymatic activity to hydrolyze nucleotides like ATP and GTP to generate energy for polymerization. Therefore, the formation of intermediate filaments is multistep self-assembly. The involvement of any accessory proteins in intermediate filament formation has not yet been reported.

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...