Written by Dr. Chandrakanth Edamakanti Edited by Dr. Hayley McLoughlin
Recent study decodes the protein signature of toxic Purkinje cells, finding that Purkinje cell mTORC1 signaling is impaired in SCA1.
Spinocerebellar ataxia type 1 (SCA1) is a late onset cerebellar neurodegenerative disorder caused by a mutation (in this case, an abnormal polyglutamine stretch) in the Ataxin-1 gene. People with this condition experience problems with coordination and balance, a set of symptoms known as ataxia. The protein produced by this faulty gene, ATXN1, is particularly toxic to the Purkinje cells, the sole output neurons of the cerebellum. However, the reason behind the selective toxicity of Purkinje cells in SCA1 is unknown.
The main focus of this article is to address this question. It is the first study to find the protein signature of toxic Purkinje cells in SCA1 mice. In the end, the authors identified widespread protein changes that are associated with Purkinje cell toxicity.
Written by Dr. Hannah K Shorrock Edited by Dr. Judit M Perez Ortiz
How one team uncovered the first SCA known to be caused by a CTG repeat expansion mutation
Identifying the gene that causes a type of ataxia not only gives patients and their families a clearer diagnosis and prognosis, but also allows scientists to model the disease. Through genetic animal models of ataxia, researchers can study how a single mutation causes a disease and how we can try to slow, halt, or even reverse this process. It is this path through research that may eventually lead from gene discovery to the development of effective therapies.
The gene that causes spinocerebellar ataxia type 8 (SCA8) was first described in a research article published in 1999. Since then, many research articles on SCA8 have been published, including research into the DNA repeat expansions that cause the ataxia, the cellular processes that lead to ataxia, and the development of multiple animal models of SCA8. Together, these move the scientific community further along the road of research.
About six months ago, scientists from all over the world converged on the 2018 Ataxia Investigators Meeting. Colleagues and students discussed the latest advancements in ataxia research. Researchers were able to connect with patients and families, letting them know what progress was being made.
Some of the discussion between trainees at this meeting highlighted how great it was to be able to speak with patients and let them know what was happening in the lab. It was unfortunate that this opportunity only happened every two years.
It was at this meeting where the idea for SCAsource was born: a website where scientific articles on SCAs and related ataxias would be translated into plain language that anyone would be able to understand.
Written By Dr. Marija Cvetanovic Edited by Dr. Sriram Jayabal
Protein kinase C: one protein that may help to protect against cerebellar neuronal dysfunction & death in spinocerebellar ataxias
Among the estimated 86 billion brain cells (known as “neurons”) in the human body (Azevedo et al., 2009), there is a small population of cells called Purkinje neurons. Though they only constitute a modest ~14-16 million cells, (Nairn et al., 1989), death or dysfunction in Purkinje neurons can cause you to lose your ability to walk coherently – a clinical symptom known as “ataxia.” This is because Purkinje neurons are the major work horse of the cerebellum, which is the part of the brain that fine-tunes our movement. While different types of hereditary spinocerebellar ataxias (SCAs) are caused by mutations in different genes, they all exhibit one thing in common: Purkinje neurons undergo severe degeneration. Neither the reasons for this selective vulnerability of Purkinje neurons in ataxia, nor howto increase their resistance to degeneration, are clear.
Written by Logan Morrison Edited by Dr. Hayley McLoughlin
Research group uncovers the key molecular interaction that causes spinocerebellar ataxia type 1 (SCA1).
When we talk and think about human disease, it is natural to focus on causes. For some disorders, the source of the problem is clear: there’s no question why a patient with a spinal cord injury has paralysis, for instance. Other diseases, like schizophrenia, are incredibly difficult to attribute to specific environmental influences or genetic mutations (probably because they are the result of a variety of subtle factors that add up to cause the disorder).
Our current understanding of spinocerebellar ataxia type 1 (SCA1) falls somewhere in between these extremes. For years, we have known that SCA1 is caused by a polyglutamine expansion in the ataxin-1 gene. In short, this means that SCA1 patients have experienced a rare copying error in their genetic code in the region that is responsible for guiding the production of the Ataxin-1 protein (ATXN1). However, there are still quite a few questions surrounding what ATXN1 does under normal circumstances. This has meant that, so far, scientists have not been able to show why a polyglutamine expansion in the ataxin-1 gene causes the cells of the cerebellum, spine, and brainstem to lose their normal function in cases of SCA1.