: 149–165  Among other interactions, it forms a transcription complex with Retinoid-related Orphan nuclear-receptor transcription factor α (RORα) following interactions with an activator, Histone acetyltransferase KAT5, sometimes referred to as TIP60, and it is in the signaling mediated by metabotropic glutamate receptor 1 (mGluR1). Resonant Recognition Modeling of the ataxin 1 protein has shown possible binding sites for growth factor independent transcription repressor 1 (Gfi-1). The predictions of this computational model reveal an interaction that could play a role in SCA1 pathology, because the Gfi-1 protein is known to cause selective degradation of Purkinje cells. : 149–165  It is the extensive involvement of ataxin 1 in many different functions that make understanding the biochemical pathophysiology of its mutant form difficult to identify and understand. : 15 The mechanism by which expanded CAG repeat regions in ataxin 1 cause neuronal degeneration is unclear. It was historically believed to be caused by aggregation and deposition of the affected protein similar to other polyglutamine expansion diseases, however rodent model studies have shown significantly later formation of nuclear inclusions of mutant proteins in cerebellum and spinal cord neurons than in cortical and hippocampal neurons, which typically show only mild degeneration in SCA1 persons, suggesting a more complicated mechanism. Ataxin-null mice are shown to exhibit reduced motor and spatial learning, suggesting ataxin 1 plays a role in synaptic plasticity and interactions between the motor neurons and the hippocampus.
Cell replacement therapies
One treatment option being investigated is stem cell therapy, which attempts to replace dead tissue by transplanting stem cells into affected region and either stimulating them to differentiate into the desired cell types or allowing them to stimulate endogenous regenerative mechanisms. These techniques are of interest to researchers as a possible treatment for neurodegenerative diseases, but currently are of limited success in animal models, and in in-vitro cell culture studies. The ability for grafted cells to integrate into the desired tissue and adjust for the unique pathologies of different neurodegenerative disorders can be a severe limitation on the development of stem cell based treatments. Further, the tissues in the brain often rely on intricate and complicated arrangements of neurons; regions of the brain that do not require precision in these patterns to function, like the striatum affected by Parkinsons disease which uses paracrine signaling, tend to have better results in stem cell therapies than systems that require precision, like the cerebellum and pons. Stem cell therapies can be especially difficult in replacing Purkinje neuron loss as unaffected granule cells can prevent axons reaching the deep cerebellar nuclei with which Purkinje cells interface. Despite these difficulties, grafted neural precursor cells have been shown to be viable and to successfully migrate into desired location in SCA1 transgenic mice models and mesenchymal stem cells have been shown to mitigate loss of dendritic arborization SCA1 mice.