Tanaka, MT;
Miki, Y;
Bettencourt, C;
Ozaki, T;
Tanji, K;
Mori, F;
Kakita, A;
(2022)
Involvement of autophagic protein DEF8 in Lewy bodies.
Biochemical and Biophysical Research Communications
, 623
pp. 170-175.
10.1016/j.bbrc.2022.07.069.
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Abstract
Dysregulation of autophagy, one of the major processes through which abnormal proteins are degraded, is a cardinal feature of synucleinopathies, including Lewy body diseases [Parkinson's disease (PD) and dementia with Lewy bodies (DLB)] and multiple system atrophy (MSA), which are characterized by the presence of abnormal α-synuclein in neurons and glial cells. Although several research groups have reported that Rubicon family proteins can regulate autophagosome-lysosome fusion or positioning, little is known about their involvement in synucleinopathies. In the present study, by studying patients with PD (N = 8), DLB (N = 13), and MSA (N = 5) and controls (N = 16), we explored the involvement of Rubicon family proteins [Rubicon, Pacer and differentially expressed in FDCP8 (DEF8)] in synucleinopathies. Immunohistochemical analysis showed that not only brainstem-type Lewy bodies but also cortical Lewy bodies were immunoreactive for DEF8 in Lewy body diseases, whereas Rubicon and Pacer were detectable in only a few brainstem-type Lewy bodies in PD. Glial cytoplasmic inclusions in patients with MSA were not immunoreactive for Rubicon, Pacer or DEF8. Immunoblotting showed significantly increased protein levels of DEF8 in the substantia nigra and putamen of patients with PD and the temporal cortex of patients with DLB. In addition, the smear band of DEF8 appeared in the insoluble fraction where that of phosphorylated α-synuclein was detected. These findings indicate the involvement of DEF8 in the formation of Lewy bodies. Quantitative and qualitative alterations in DEF8 may reflect the dysregulation of autophagy in Lewy body diseases.
| Type: | Article |
|---|---|
| Title: | Involvement of autophagic protein DEF8 in Lewy bodies |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.bbrc.2022.07.069 |
| Publisher version: | https://doi.org/10.1016/j.bbrc.2022.07.069 |
| 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: | Autophagy, DEF8, Dementia with Lewy bodies, Parkinson's disease, Synucleinopathy, α-synuclein, Autophagy, Brain, Humans, Intracellular Signaling Peptides and Proteins, Lewy Bodies, Lewy Body Disease, Multiple System Atrophy, Parkinson Disease, Synucleinopathies, alpha-Synuclein |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10157092 |
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