Blocking IL-6 signaling prevents astrocyte-induced neurodegeneration in an iPSC-based model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease associated with progressive death of midbrain dopamine (DAn) neurons in the substantia nigra (SN). Since it has been proposed that patients with PD exhibit an overall proinflammatory state, and since astrocytes are key mediators of the inflammation response in the brain, here we sought to address whether astrocyte-mediated inflammatory signaling could contribute to PD neuropathology. For this purpose, we generated astrocytes from induced pluripotent stem cells (iPSCs) representing patients with PD and healthy controls.

Dissecting the non-neuronal cell contribution to Parkinson's disease pathogenesis using induced pluripotent stem cells.

Parkinson's disease (PD) is an incurable age-linked neurodegenerative disease with characteristic movement impairments that are caused by the progressive loss of dopamine-containing neurons (DAn) within the substantia nigra pars compacta. It has been suggested that misfolded protein aggregates together with neuroinflammation and glial reactivity, may impact nerve cell function, leading to neurodegeneration and diseases, such as PD. However, not many studies have been able to examine the role of human glial cells in the pathogenesis of PD.

Parkinsonian neurotoxicants impair the anti-inflammatory response induced by IL4 in glial cells: involvement of the CD200-CD200R1 ligand-receptor pair.

Exposure to pesticides such as rotenone is a risk factor for Parkinson's disease. Dopaminergic neurons are especially sensitive to the toxicity of compounds that inhibit the mitochondrial respiratory chain such as rotenone and 1-methyl-4-phenylpyridinium (MPP+). However, there is scarce information on their effects on glia.