Israeli researchers spot Parkinson's nerve cell processes - study

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"New research conducted at the University of Haifa has identified for the first time a number of neural processes that are common to various different types of Parkinson’s disease (PD). ...
The processes relate to the ability of cells to connect to the extracellular matrix and their capacity to create new synopses. Thanks to the use of the innovative “Sendai Reprogramming” technique, the researchers were able to show for the first time that even in sporadic Parkinson patients for which no animal model has yet been developed, these processes are also impaired. ..."

From the abstract:

"Several mutations that cause Parkinson’s disease (PD) have been identified over the past decade. These account for 15-25% of PD cases; the rest of the cases are considered sporadic. ... While rodent models exist for some of the PD-causing mutations, research on the sporadic forms of PD is lagging due to a lack of cellular models. In our study, we differentiated PD patient-derived dopaminergic (DA) neurons from induced pluripotent stem cells (iPSCs) of several PD-causing mutations as well as from sporadic PD patients. Strikingly, we observed a common neurophysiological phenotype: Neurons derived from PD patients had a severe reduction in the rate of synaptic currents compared to those derived from healthy controls. While the relationship between mutations in genes such as the SNCA and LRRK2 and a reduction in synaptic transmission has been investigated before, here we show evidence that the pathogenesis of the synapses in neurons is a general phenotype in PD. Analysis of RNA sequencing results displayed changes in gene expression in different synaptic mechanisms as well as other affected pathways such as extracellular matrix-related pathways. Some of these dysregulated pathways are common to all PD patients (monogenic or idiopathic). Our data, therefore, shows changes that are central and convergent to PD and suggests a strong involvement of the tetra-partite synapse in PD pathophysiology."

Israeli researchers spot Parkinson's nerve cell processes - study - The Jerusalem Post: One of the problems in developing treatments is the fact that only 15% of Parkinson’s cases are caused by known genetic factors.

Reduced synaptic activity and dysregulated extracellular matrix pathways are common phenotypes in midbrain neurons derived from sporadic and mutation-associated Parkinson’s disease patients (preprint, open access)

Shani Stern, lead author of the study