Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/88470
Title: Intracellular and Intercellular Mitochondrial Dynamics in Parkinson's Disease
Authors: Valdinocci, Dario
Simões, Rui F. 
Kovarova, Jaromira 
Cunha-Oliveira, Teresa 
Neuzil, Jiri 
Pountney, Dean L
Keywords: Parkinson’s; alpha-synuclein; mitochondria; mitophagy; tunneling nanotube
Issue Date: 18-Sep-2019
Serial title, monograph or event: Frontiers in Neuroscience
Issue: 13:930
Abstract: The appearance of alpha-synuclein-positive inclusion bodies (Lewy bodies) and the loss of catecholaminergic neurons are the primary pathological hallmarks of Parkinson's disease (PD). However, the dysfunction of mitochondria has long been recognized as a key component in the progression of the disease. Dysfunctional mitochondria can in turn lead to dysregulation of calcium homeostasis and, especially in dopaminergic neurons, raised mean intracellular calcium concentration. As calcium binding to alpha-synuclein is one of the important triggers of alpha-synuclein aggregation, mitochondrial dysfunction will promote inclusion body formation and disease progression. Increased reactive oxygen species (ROS) resulting from inefficiencies in the electron transport chain also contribute to the formation of alpha-synuclein aggregates and neuronal loss. Recent studies have also highlighted defects in mitochondrial clearance that lead to the accumulation of depolarized mitochondria. Transaxonal and intracytoplasmic translocation of mitochondria along the microtubule cytoskeleton may also be affected in diseased neurons. Furthermore, nanotube-mediated intercellular transfer of mitochondria has recently been reported between different cell types and may have relevance to the spread of PD pathology between adjacent brain regions. In the current review, the contributions of both intracellular and intercellular mitochondrial dynamics to the etiology of PD will be discussed.
URI: http://hdl.handle.net/10316/88470
ISSN: 1662-4548
DOI: 10.3389/fnins.2019.00930
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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