Huntington’s disease (HD) is an autosomal-dominant neurodegenerative disorder that can cause motor symptoms, cognitive dysfunction, and psychiatric disorder. The typical symptom of HD is chorea, affected by the disease, the HD patients will be temporarily uncontrollable grimacing, nodding, and finger beating, and even worse, typical dance-like involuntary movements, and difficulty swallowing (Burgunder
2015). An MRI of HD shows damaged caudate and global atrophy dominated by the frontal lobe (Goh
et al. 2018). The exact mechanism of HD pathogenesis is currently unknown, but the pathogenic gene
HTT has been recognized (Nakamura
1993). A mutation in the
HTT gene can cause an abnormal expansion of a polyglutamine (polyQ) repeat at the amino terminus of Huntingtin (HTT) protein, which results in HD (Finkbeiner
2011; Nakamura
1993). HTT is a 348 kDa protein that plays important role in embryonic development and various cellular activities (Saudou and Humbert
2016). On the one hand, the cryo-EM structure of full-length human HTT in a complex was demonstrated (Guo
et al. 2018). On the other hand, there are also many researchers focusing on protein aggregation
in situ. Li
et al. used electron microscopic immunocytochemistry to identify the HTT aggregation in HD mouse model (Li
et al. 2001). In 2017, Bäuerlein
et al. found that polyQ inclusions are composed of amyloid-like fibrils interacting with cellular endo-membranes, especially the endoplasmic reticulum (ER) (Bäuerlein
et al. 2017). Their results suggested the previous study that wild-type HTT has an interaction with cellular membranes (Kegel-Gleason
2013), and fibrils of polyQ-expanded HTT exon 1 and other amyloids can cause membrane disruption (Milanesi
et al. 2012; Pieri
et al. 2012). In addition, HTT expression can lead to the accumulation of brain iron in human HD (Rosas
et al. 2012), and indicates it is ferrous (II) iron that contributes to this accumulation rather than ferric (III) iron (
Fig. 5) (Chen
et al. 2013).