Astrocytes are incredibly versatile cells of the nervous system. Throughout the life of an individual, these cells harbor a variety of different roles, from metabolic and trophic neuronal support to the coordination of the brain inflammatory response. Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder characterized by a variety of pathological events, including neuronal and astrocytic pathological phenotypes. While the effects of PD on neurons is under active investigation, little is known about its impact on astrocytes. Modeling the LRRK2 G2019S familial form of PD using iPSC-based technologies, we demonstrate that secretion of extracellular vesicles (EVs) is dysregulated in PD astrocytes. Furthermore, EVs secreted by these patient-derived astrocytes are mislocalized in recipient neurons, and fail to provide neurotrophic support to dopaminergic neurons. Therefore, while studies on PD have largely been focused on cell-autonomous mechanisms of neuron degeneration, a new framework emerges and suggests to embrace the contributions of astrocytes and astrocyte-to-neuron communication to PD pathology.

The blood-brain barrier (BBB) regulates exchanges between the central nervous system and the peripheral circulation to maintain brain homeostasis, and relies on the coordinated action of brain microvascular endothelial cells (BMECs), pericytes and astrocytes. In Parkinson’s disease (PD), a neurodegenerative disorder characterized by neuronal death and astrocyte reactivity, barrier integrity is compromised which may further contribute to disease progression. The objective of this work is to determine how astrocytes with the PD-related mutation LRRK2 G2019S affect the functionality of the BBB.

Recent advances in pharmacology and disease modeling have opened unprecedented avenues for the exploration of bioactive botanical extracts. In this context, the study of Indigenous traditional medicines revealed medicinal plants with remarkable neuroprotective activities in Parkinson’s disease models. For example, extracts prepared from berries, garlic, elderflower and other plants protected neurons from degeneration. The generation of neurons and astrocytes from patient-derived induced pluripotent stem cells (iPSCs) allows for the first time to test the pro-health activities of botanical extracts on cells that closely resemble patient cells. These patient-like cells, or “disease in a dish”, hold the promises for more translational results and a better understanding of the complex interactions between cells types in Parkinson’s disease. Furthermore by combining iPSC-derived cells and advances in sequencing technologies, we are entering an exciting era of high-throughput transcriptome screening that will reveal new biological effects of traditional medicines and shed light on their untapped potential.