Abstract Extracellular vesicles (EVs) are emerging as powerful players in cell‐to‐cell communication both in healthy and diseased brain. In Parkinson's disease (PD)—characterized by selective dopaminergic neuron death in ventral midbrain (VMB) and degeneration of their terminals in striatum (STR)—astrocytes exert dual harmful/protective functions, with mechanisms not fully elucidated. Here, this study shows that astrocytes from the VMB‐, STR‐, and VMB/STR‐depleted brains release a population of small EVs in a region‐specific manner. Interestingly, VMB‐astrocytes secreted the highest rate of EVs, which is further exclusively increased in response to CCL3, a chemokine that promotes robust dopaminergic neuroprotection in different PD models. The neuroprotective potential of nigrostriatal astrocyte‐EVs is investigated in differentiated versus undifferentiated SH‐SY5Y cells exposed to oxidative stress and mitochondrial toxicity. EVs from both VMB‐ and STR‐astrocytes counteract H 2 O 2 ‐induced caspase‐3 activation specifically in differentiated cells, with EVs from CCL3‐treated astrocytes showing a higher protective effect. High resolution respirometry further reveals that nigrostriatal astrocyte‐EVs rescue neuronal mitochondrial complex I function impaired by the neurotoxin MPP + . Notably, only EVs from VMB‐astrocyte fully restore ATP production, again specifically in differentiated SH‐SY5Y. These results highlight a regional diversity in the nigrostriatal system for the secretion and activities of astrocyte‐EVs, with neuroprotective implications for PD.
A novel community driven software for functional enrichment analysis of extracellular vesicles data
ABSTRACTBioinformatics tools are imperative for the in depth analysis of heterogeneous high‐throughput data. Most of the software tools are developed by specific laboratories or groups or companies wherein they are designed to perform the required analysis for the group. However, such software tools may fail to capture “what the community needs in a tool”. Here, we describe a novel community‐driven approach to build a comprehensive functional enrichment analysis tool. Using the existing FunRich tool as a template, we invited researchers to request additional features and/or changes. Remarkably, with the enthusiastic participation of the community, we were able to implement 90% of the requested features. FunRich enables plugin for extracellular vesicles wherein users can download and analyse data from Vesiclepedia database. By involving researchers early through community needs software development, we believe that comprehensive analysis tools can be developed in various scientific disciplines.