TY - JOUR
T1 - Mitochondrial-Derived Vesicles as Candidate Biomarkers in Parkinson's Disease: Rationale, Design and Methods of the EXosomes in PArkiNson Disease (EXPAND) Study
AU - Picca, Anna
AU - Guerra, Flora
AU - Calvani, Riccardo
AU - Bucci, Cecilia
AU - Lo Monaco, Maria Rita
AU - Bentivoglio, Anna Rita
AU - Landi, Francesco
AU - Bernabei, Roberto
AU - Marzetti, Emanuele
PY - 2019
Y1 - 2019
N2 - The progressive loss of dopaminergic neurons in the nigro-striatal system is a major trait of Parkinson's disease (PD), manifesting clinically as motor and non-motor symptoms. Mitochondrial dysfunction and oxidative stress are alleged pathogenic mechanisms underlying aggregation of misfolded α-synuclein that in turn triggers dopaminergic neurotoxicity. Peripheral processes, including inflammation, may precede and contribute to neurodegeneration. Whether mitochondrial dyshomeostasis in the central nervous system and systemic inflammation are linked to one another in PD is presently unclear. Extracellular vesicles (EVs) are delivery systems through which cells can communicate or unload noxious materials. EV trafficking also participates in mitochondrial quality control (MQC) by generating mitochondrial-derived vesicles to dispose damaged organelles. Disruption of MQC coupled with abnormal EV secretion may play a role in the pathogenesis of PD. Furthermore, due to its bacterial ancestry, circulating mitochondrial DNA can elicit an inflammatory response. Therefore, purification and characterisation of molecules packaged in, and secreted through, small EVs (sEVs)/exosomes in body fluids may provide meaningful insights into the association between mitochondrial dysfunction and systemic inflammation in PD. The EXosomes in PArkiNson Disease (EXPAND) study was designed to characterise the cargo of sEVs/exosomes isolated from the serum of PD patients and to identify candidate biomarkers for PD.
AB - The progressive loss of dopaminergic neurons in the nigro-striatal system is a major trait of Parkinson's disease (PD), manifesting clinically as motor and non-motor symptoms. Mitochondrial dysfunction and oxidative stress are alleged pathogenic mechanisms underlying aggregation of misfolded α-synuclein that in turn triggers dopaminergic neurotoxicity. Peripheral processes, including inflammation, may precede and contribute to neurodegeneration. Whether mitochondrial dyshomeostasis in the central nervous system and systemic inflammation are linked to one another in PD is presently unclear. Extracellular vesicles (EVs) are delivery systems through which cells can communicate or unload noxious materials. EV trafficking also participates in mitochondrial quality control (MQC) by generating mitochondrial-derived vesicles to dispose damaged organelles. Disruption of MQC coupled with abnormal EV secretion may play a role in the pathogenesis of PD. Furthermore, due to its bacterial ancestry, circulating mitochondrial DNA can elicit an inflammatory response. Therefore, purification and characterisation of molecules packaged in, and secreted through, small EVs (sEVs)/exosomes in body fluids may provide meaningful insights into the association between mitochondrial dysfunction and systemic inflammation in PD. The EXosomes in PArkiNson Disease (EXPAND) study was designed to characterise the cargo of sEVs/exosomes isolated from the serum of PD patients and to identify candidate biomarkers for PD.
KW - exosomes
KW - extracellular vesicles
KW - mitochondrial quality control
KW - mitochondrial-lysosomal axis
KW - mitophagy
KW - mtDNA
KW - exosomes
KW - extracellular vesicles
KW - mitochondrial quality control
KW - mitochondrial-lysosomal axis
KW - mitophagy
KW - mtDNA
UR - http://hdl.handle.net/10807/219480
U2 - 10.3390/ijms20102373
DO - 10.3390/ijms20102373
M3 - Article
SN - 1422-0067
VL - 20
SP - 1
EP - 13
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
ER -