“…In fact, an important interference was attributed to sequestration and depletion of p97/VCP and its cofactors Npl4 and Ufd1 by mHtt, which would not cause global UPS deficiency, but rather a crippling dysfunction of ERAD (Duennwald and Lindquist, 2008; Yang et al, 2010; Leitman et al, 2013). Homocysteine-induced endoplasmic reticulum protein (Herp), an important factor in ERAD, was recently reported to be directly involved in targeting of mHtt for degradation (Luo et al, 2018). The inhibition of ERAD leads to accumulation of unfolded proteins in the ER, ER stress, and UPR induction, which were observed in HD models in yeast and mammalian cells (Duennwald and Lindquist, 2008; Reijonen et al, 2008; Carnemolla et al, 2009; Leitman et al, 2013, 2014), in animal HD models (Carnemolla et al, 2009; Cho et al, 2009; Noh et al, 2009; Vidal et al, 2012), and in post-mortem samples from HD patients (Carnemolla et al, 2009).…”