These animals have been engineered to express the disease-associated proteins huntingtin and ataxin-3.
elegans through neuronal expression of polyglutamine-expanded ataxin-3 protein.
38) Fluorescent fusion proteins of Ataxin-3
(disease protein of spinocerebellar ataxia type-3) and huntingtin (disease protein of Huntington's disease) recover after photobleaching was very slow, while FLIP did not show protein release from aggregates.
The Usp9x, Usp30, Usp36, and ataxin-3
may preserve mitochondrial protein degradation by editing or removing the degradative ubiquitin signal [113, 136-138].
In these mice, the orexin promoter drives expression of the neurodegenerative gene ataxin-3
and leading to progressive loss of the orexin neurons during development.
Similarly, the expansion of glutamine residues in ataxin-3
leads to Machado-Joseph disease, which is a neurodegenerative disorder that occurs due to the accumulation of this toxic protein in the nucleus and the mitochondria.
The present proposal aims to study the relationships existing between protein structural dynamics and pathological aggregation of the multidomain N-terminal part of the polyglutamine (polyQ) protein ataxin-3
Various reported substrates of parkin include CDC-rel-1, O-glycosylated a-synuclein, the parkin-associated endothelin-like receptor, the [alpha]-synuclein--binding protein synphilin-1, actin filaments, the poly(Q)expanded mutant of ataxin-3
, Huntington disease polyglutamine proteins, the amyloidogenic Alzheimer disease A[beta] 1-42 peptide (amyloid-[beta] peptide 1-42), and a[beta]-tubulin.
mitigates degeneration in a rat model of Machado-Joseph disease: no role for wild-type ataxin-3
The cause of the disease is a recurring genetic sequence in the ataxin-3
gene which leads to agglutination of the corresponding protein and as a result, the nerve cells in the brain become damaged eventually.
In each case, antibodies showed that the mutant form of the protein ataxin-3
had formed large masses inside the nuclei of some brain cells.