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Exosome Release Is Modulated by the Mitochondrial-Lysosomal Crosstalk in Parkinson’s Disease Stress Conditions

Currim, F; Singh, J; Shinde, A; Gohel, D; Roy, M; Singh, K; Shukla, S; ... Singh, R; + view all (2021) Exosome Release Is Modulated by the Mitochondrial-Lysosomal Crosstalk in Parkinson’s Disease Stress Conditions. Molecular Neurobiology , 58 (4) pp. 1819-1833. 10.1007/s12035-020-02243-3. Green open access

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Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta region of the brain. The main pathological hallmark involves cytoplasmic inclusions of α-synuclein and mitochondrial dysfunction, which is observed in other part of the central nervous system other than SN suggesting the spread of pathogenesis to bystander neurons. The inter-neuronal communication through exosomes may play an important role in the spread of the disease; however, the mechanisms are not well elucidated. Mitochondria and its role in inter-organellar crosstalk with multivesicular body (MVB) and lysosome and its role in modulation of exosome release in PD is not well understood. In the current study, we investigated the mitochondria-lysosome crosstalk modulating the exosome release in neuronal and glial cells. We observed that PD stress showed enhanced release of exosomes in dopaminergic neurons and glial cells. The PD stress condition in these cells showed fragmented network and mitochondrial dysfunction which further leads to functional deficit of lysosomes and hence inhibition of autophagy flux. Neuronal and glial cells treated with rapamycin showed enhanced autophagy and inhibited the exosomal release. The results here suggest that maintenance of mitochondrial function is important for the lysosomal function and hence exosomal release which is important for the pathogenesis of PD.

Type: Article
Title: Exosome Release Is Modulated by the Mitochondrial-Lysosomal Crosstalk in Parkinson’s Disease Stress Conditions
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s12035-020-02243-3
Publisher version: https://doi.org/10.1007/s12035-020-02243-3
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Mitochondrial dysfunctions, Mitochondria-lysosome crosstalk, Exosome release, Parkinson’s disease
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10166415
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