Synphilin-1 transgenic mice exhibit mild motor impairments.

Synphilin-1 represents a cytoplasmic protein that interacts with alpha-synuclein and localizes close to synaptic vesicles. The interaction of synphilin-1 with several proteins involved in Parkinson's disease suggests that it might be involved in the pathogenesis of the disease. Nonetheless, the function of synphilin-1 remains unclear.

White matter lesions in the brain with frontotemporal lobar degeneration with motor neuron disease: TDP-43-immunopositive inclusions co-localize with p62, but not ubiquitin.

Recently, TDP-43 was established as a major component of the ubiquitinated inclusions found in both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with motor neuron disease (FTLD-MND). However, differences in the underlying pathogenesis between ALS and FTLD-MND remain yet to be elucidated. Originally, TDP-43-immunopositive inclusions were found in neuronal cells and reported to be ubiquitinated.

Abundance of aspargynyl-hydroxylase FIH is regulated by Siah-1 under normoxic conditions.

The activity of hypoxia-inducible factors-1alpha (HIF-1alpha) is regulated by two types of hydroxylases, prolyl-hydroxylase (PHD) and aspargynyl-hydroxylase factor inhibiting HIF-1alpha (FIH). Hydroxylation of HIF-1alpha by PHD and FIH causes proteasomal degradation and transcriptional inhibition of HIF-1alpha, respectively. Siah ubiquitin ligases regulate the abundance of PHD via targeting for proteasomal degradation.

Siah-1 facilitates ubiquitination and degradation of factor inhibiting HIF-1alpha (FIH).

Hypoxia-inducible factor-1alpha (HIF-1alpha) has a central role in neuroprotective responses to hypoxia in the brain. Hydroxylation of HIF-1alpha by prolyl-hydroxylase PHD and aspargynyl-hydroxylase FIH (factor inhibiting HIF-1alpha) causes proteasomal degradation and transcriptional inhibition of HIF-1alpha. Siah ubiquitin ligases regulate the abundance of PHD via targeting for proteasomal degradation.

Hypoxia-induced upregulation of endothelial small G protein RhoA and Rho-kinase/ROCK2 inhibits eNOS expression.

The small G protein RhoA and its downstream effector Rho-kinase/ROCK2 play an important role in regulation of various vasculature cellular functions. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is an important mediator of vascular homeostasis and cerebral blood flow. Using the human endothelial cell line HUVEC, the present study investigated the role of RhoA and Rho-kinase in endothelial eNOS protein expression under hypoxic conditions as an in vitro model of ischemia.