Parkinson’s disease affects more than 6 million people worldwide. This neurodegenerative disease is characterized by the death of dopaminergic neurons in the substantia nigra pars compacta, with intracellular accumulation of alpha-synuclein aggregates known as Lewi bodies. This neuronal loss leads to a decrease in the neurotransmitter dopamine that cause mainly motor symptoms, like tremor, rigidity, and slowness of movement. Cognitive and behavioral problems can also appear.
However, other cells are involved in the pathological mechanism of this disease. In particular glial cells like astrocytes participate to the neuro-inflammation found in neurodegenerative disease and in alpha-synuclein regulation. Indeed pathologic alpha-synuclein release from neurons activates astrocytes, but some mutations associated to Parkinson’s disease impair lysosomal protein degradation in astrocytes and lead to the accumulation of alpha-synuclein. Moreover, the oxidative stress results in the release of pro-inflammatory mediators from astrocytes, and also unknown toxins that promote dopaminergic neuronal death (Kam et al. 2020).
Interestingly, neurodegenerative disease involve not only the cells but also the extracellular matrix. Indeed, its composition is altered in Parkinson’s disease, with in particular abnormal levels of glycans, including proteoglycans (van Horssen et al. 2003; Dwyer and Esko 2016; Freeze et al. 2015). Matrix modifications can impact on the biochemical signal retention or diffusion, and thus on cell response.
Face to these complex interaction between neurons, glial cells and extracellular matrix, we have realized a co-culture of dopaminergic neurons (Luhmes cell line) and astrocytes (human primary cells) in BIOMIMESYS® Brain, our 3D cell culture technology that mimics brain extracellular matrix.
If you need more information about our cerebral in vitro models in 3 dimensions, feel free to contact us!