UBNeuro researchers find a protein involved in Huntington’s disease motor deficits
Huntington’s disease is known for a mutation in the Huntingtin gen. Patients show involuntary movements, cognitive deficits and specific psychiatric disorders of the disease, which result from the degeneration and death of medium spiny striatal neurons. A study led by researchers of the Institute of Neurosciences of the UB (UBNeuro) describes the toxic role of the protein RTP801 in this pathology, and specifically, how it affects motor deficits.
“This protein was identified in Parkinson’s disease, and now we could describe it in Huntington’s, another movement disorder. When the expression of this protein is regulated downward, we prevent motor deficits from appearing”, says Cristina Malagelada, researcher at UBNeuro and one of the authors of the study, published in the journal Cell Death and Disease.
The team studied whether the protein RTP801 is involved in the deficits in the motor learning using mice models, cultured primary neurons and post mortem brain samples of patients with Huntington’s. The results of the study provide high levels of this protein in the synapsis of the striatum, both in mice models and human samples.
“The main result of the study is that the protein RTP801 contributes to the damaging effect of the mutated huntingtin in mice striatal synaptic spines that model Huntington’s disease”, notes Esther Pérez Navarro, researcher at UBNeuro and author of the study.
In the study, researchers saw that by provoking a decrease of the RTP801 protein, the crucial protein levels that are dysregulated in this pathology are restored: Akt kinase, RICTOR and TrkB. “These results validate RTP801 as a therapeutic target in Huntington’s disease. The design of molecules or therapeutic strategies to modulate levels of the protein RTP801 will be very important to find an efficient treatment to work on this disease”, concludes Malagelada.
Article reference: N. Martín-Flores et al. «Synaptic RTP801 contributes to motor-learning dysfunction in Huntington ’s disease». Cell Death & Disease, volume 11, issue number 569, 2020. Doi: 10.1038/s41419-020-02775-