Investigating Key Mechanisms Of Parkinson's With An αSyn Fibril-Induced Brain-On-A-Chip Model

In 1817, Dr. James Parkinson penned observations of a puzzling disease affecting his patients, marked by a gradual loss of motor control and an involuntary tremor. Unbeknownst to him, this condition, now termed Parkinson’s disease, stemmed from the death of dopamine-producing neurons in large parts of patients’ brains, specifically in the substantia nigra. Despite over two centuries of research, much about Parkinson’s disease remains elusive.

Central to this enigma is the protein α-synuclein. Observations suggest an abnormal accumulation of α-synuclein bundles in nerve tissues, causing inflammatory signaling, mitochondrial dysfunction, and worsening disease. While its prominence in patients with Parkinson’s disease suggests it may drive disease pathology, the mechanism remains unknown.

In order to better understand Parkinson’s disease pathology and the potential role of ɑ-synuclein, researchers require powerful disease models that enable them to observe the actions of various cell types in the substantia nigra when in the presence of ɑ-synuclein bundles. Supported in part by the Michael J. Fox Foundation for Parkinson’s Research, Emulate worked with investigators from Harvard, Northeastern University, and the University of Athens to create a dynamic "brain-on-a-chip" model that replicates the human substantia nigra with the integration of multiple cell types and microenvironments features. Continue reading to learn about the results of these efforts.