Lipids, lysosomes and mitochondria: insights into Lewy body formation from rare monogenic disorders

2021 | journal article; overview. A publication with affiliation to the University of Göttingen.

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​Lipids, lysosomes and mitochondria: insights into Lewy body formation from rare monogenic disorders​
Erskine, D.; Koss, D.; Korolchuk, V. I.; Outeiro, T. F. ; Attems, J. & McKeith, I.​ (2021) 
Acta Neuropathologica141(4) pp. 511​-526​.​ DOI: https://doi.org/10.1007/s00401-021-02266-7 

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Authors
Erskine, Daniel; Koss, David; Korolchuk, Viktor I.; Outeiro, Tiago F. ; Attems, Johannes; McKeith, Ian
Abstract
Accumulation of the protein α-synuclein into insoluble intracellular deposits termed Lewy bodies (LBs) is the characteristic neuropathological feature of LB diseases, such as Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and dementia with LB (DLB). α-Synuclein aggregation is thought to be a critical pathogenic event in the aetiology of LB disease, based on genetic analyses, fundamental studies using model systems, and the observation of LB pathology in post-mortem tissue. However, some monogenic disorders not traditionally characterised as synucleinopathies, such as lysosomal storage disorders, iron storage disorders and mitochondrial diseases, appear disproportionately vulnerable to the deposition of LBs, perhaps suggesting the process of LB formation may be a result of processes perturbed as a result of these conditions. The present review discusses biological pathways common to monogenic disorders associated with LB formation, identifying catabolic processes, particularly related to lipid homeostasis, autophagy and mitochondrial function, as processes that could contribute to LB formation. These findings are discussed in the context of known mediators of α-synuclein aggregation, highlighting the potential influence of impairments to these processes in the aetiology of LB formation.
Issue Date
2021
Journal
Acta Neuropathologica 
Project
EXC 2067: Multiscale Bioimaging 
SFB 1286: Quantitative Synaptologie 
SFB 1286 | B06: Die Rolle von RNA in Synapsenphysiologie und Neurodegeneration 
SFB 1286 | B08: Definition von Kaskaden molekularer Veränderungen bei Synucleinopathien während der Neurodegeneration 
Working Group
RG Outeiro (Experimental Neurodegeneration) 
ISSN
0001-6322
eISSN
1432-0533
Language
English

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