A new laboratory study provides clues on a particular pathway of alpha-synuclein diffusion.
Researchers have found that alpha-synuclein, a protein involved in a series of neurological disorders including Parkinson’s disease, is capable of travelling from brain to stomach and that it does so following a specific pathway. The study, carried out in rats, sheds new light on pathological processes that could underlie disease progression in humans. It was published in the journal Acta Neuropathologica.
Alpha-synuclein occurs naturally in the nervous system, where it plays an important role in synaptic function. However, in Parkinson’s disease, dementia with Lewy bodies and other neurodegenerative diseases termed “synucleinopathies”, this protein is accumulated within neurons, forming pathological aggregates. Distinct areas of the brain become progressively affected by this condition. The specific mechanisms and pathways involved in this widespread distribution of alpha-synuclein pathology remain to be fully elucidated. Clinical and experimental evidence suggests however that alpha-synuclein – or abnormal forms of it – could “jump” from one neuron to another and thus spread between anatomically interconnected regions.
Alpha-synuclein lesions have also been observed within neurons of the peripheral nervous system, such as those in the gastric wall. In some Parkinson’s patients, these lesions were detected at early disease stages.
With the help of a tailor-made viral vector the researchers triggered production of human alpha-synuclein in rats. The virus transferred the blueprint of the human alpha-synuclein gene specifically into neurons of the midbrain, which then began producing large quantities of the foreign protein, which is associated with some forms of Parkinson’s disease.
Tissue analysis by collaborators revealed that, after its midbrain expression, the protein was capable of reaching nerve endings in the gastric wall. Further work established the precise pathway used by human alpha-synuclein to complete its journey from the brain to the stomach. The protein first moved from the midbrain to the “medulla oblongata”, the lowest brainstem region; in the medulla oblongata, it was detected within neurons whose long fibers form the “vagus nerve”. Fibers of the vagus nerve connect the brain to a variety of internal organs; travelling within these fibers, human alpha-synuclein was ultimately able to reach the gastric wall about six months after its initial midbrain expression. Progressive accumulation of human alpha-synuclein within gastric nerve terminals was accompanied by evidence of neuronal damage.
Paper: “Brain-to-stomach transfer of α-synuclein via vagal preganglionic projections”
Reprinted from materials provided by DZNE.