A study led at Vall d’Hebron Institute of Research (VHIR) has demonstrated that the pathological forms of alpha-Synuclein protein extracted from patients who died with Parkinson Disease have the capacity to initiate and spread the same neurodegenerative process in mice and monkeys. The finding, published in the cover of the March issue of Annals of Neurology, may have important implications for the development of disease-modifying therapies to stop Parkinson Disease aimed at targeting expression levels, pathological conversion, and cell-to-cell transmission of alpha-Synuclein.
Recent studies concluded that synthetic alpha-Synuclein forms are toxics for neurons, both in in vitro models (cell cultures) and in vivo animal models (mice), and that can be transmitted cell-to-cell. However, it was still uncertain whether the pathogenic effects of this synthetic protein may apply to the human pathological alpha-Synuclein and occur in species closer to humans.
In this study, led by Dr. Miquel Vila, head of the Neurodegenerative Diseases group at Vall d’Hebron Institute of Research (VHIR) and member of CIBERNED, and with the participation of two additional groups from CIBERNED, and a group from the Université de Bordeaux in France , researchers extracted alpha-Synuclein aggregates from patients who died with Parkinson Disease to inoculate them in the brain of mice and monkeys.
Four months after the inoculation in mice and nine months later in monkeys, the animals started the neurodegenerative process, starting at striatal dopaminergic terminals. With these results, Dr. Vila concludes that “human pathological alpha-Synuclein aggregates trigger in mice and monkeys the same neurodegeneration process than Parkinson Disease”.