New Insights into the Molecular Basis of Ataxia
People with ataxia often experience stress-induced motor incoordination. Researchers have now discovered which receptor is responsible for this.
Published: 10.10.2025
Researchers at Ruhr University Bochum, Germany, identified a Receptor that plays a crucial role in stress-induced motor incoordination associated with ataxias. These hereditary motor disorders have long been linked to the Neurotransmitter norepinephrine. The team, led by Dr. Pauline Bohne and Professor Melanie Mark from the Behavioral Neurobiology Working Group in Bochum, has now shown that the α1D norepinephrine receptor in the Cerebellum is responsible for the symptoms. The team reports on these findings in the journal Cellular and Molecular Life Sciences from October 6, 2025.
Receptor
A receptor is a protein, usually located in the cell membrane or inside the cell, that recognizes a specific external signal (e.g., a neurotransmitter, hormone, or other ligand) and causes the cell to trigger a defined response. Depending on the type of receptor, this response can be excitatory, inhibitory, or modulatory.
Neurotransmitter
A neurotransmitter is a chemical messenger, an intermediary substance. It is released by the sender neuron at the sites of cell-cell communication and has an excitatory or inhibitory effect on the receiver neuron.
Cerebellum
Cerebellum
The cerebellum is an important part of the brain, located at the back of the brain stem and below the occipital lobe. It consists of two cerebellar hemispheres covered by the cerebellar cortex and plays an important role in motor processes, among other things. It develops from the rhombencephalon.
The messenger substance norepinephrine plays a decisive role.
People with Ataxia experience recurring episodes of motor incoordination, also known as dystonia. These phases are triggered by various factors, such as physical or emotional stress, fever, alcohol, or caffeine. The episodes are triggered by the release of norepinephrine in the cerebellum, which is the most important brain region for coordinating movement. Currently, there is no cure for ataxia. Therefore, researchers want to gain a better understanding of the underlying mechanisms to find new treatment approaches.
The researchers in Bochum investigated the role of norepinephrine receptors in mice with ataxia-like movement disorders. Previous research has shown that stress-induced dystonia is associated with irregular activity of certain nerve cells, the Purkinje cells in the Cerebellum. The researchers have now demonstrated that the α1D Receptor plays a pivotal role in this process. When the scientists switched off the receptor, either genetically or pharmacologically, the mice experienced few or no episodes of dystonia. Blocking the receptor with a specific active substance furthermore restored normal activity of the Purkinje cells.
Ataxia
A medical umbrella term for the disturbance or loss of coordination of movement. In the case of target ataxia, for example, a targeted grasp of an object may be slow, shaky, or too fast. Ataxia can be congenital or the result of lesions or degeneration.
Cerebellum
Cerebellum
The cerebellum is an important part of the brain, located at the back of the brain stem and below the occipital lobe. It consists of two cerebellar hemispheres covered by the cerebellar cortex and plays an important role in motor processes, among other things. It develops from the rhombencephalon.
Receptor
A receptor is a protein, usually located in the cell membrane or inside the cell, that recognizes a specific external signal (e.g., a neurotransmitter, hormone, or other ligand) and causes the cell to trigger a defined response. Depending on the type of receptor, this response can be excitatory, inhibitory, or modulatory.
Potential new therapeutic approach
“We hope that with the α1D receptor, we have found a new approach to prevent stress-induced dystonia in patients with Ataxia type 2,” says Pauline Bohne. However, further studies are needed to determine if the results can be applied to humans and thus to the clinic.
Ataxia
A medical umbrella term for the disturbance or loss of coordination of movement. In the case of target ataxia, for example, a targeted grasp of an object may be slow, shaky, or too fast. Ataxia can be congenital or the result of lesions or degeneration.
Original publication
Pauline Bohne, Mareike Josten, Lina Rambuscheck, Jana Brüggemann, Xinran Zhu, Max O. Rybarski and Melanie D. Mark: Cerebellar α1D- adrenergic receptors mediate stress-induced dystonia in totteringtg/tg 3 mice, in: Cellular and Molecular Life Sciences, 2025, DOI: 10.1007/s00018-025-05843-1
