Dynactin is involved in Lewy body pathology

Chang Shen, Hiroyuki Honda, Satoshi O. Suzuki, Norihisa Maeda, Masahiro Shijo, Hideomi Hamasaki, Naokazu Sasagasako, Naoki Fujii, Toru Iwaki

Research output: Contribution to journalArticle

Abstract

Dynactin forms a protein complex with dynein that retrogradely transports cargo along microtubules. Dysfunction of this dynein-dynactin complex causes several neurodegenerative diseases such as Perry syndrome, motor neuron diseases and progressive supranuclear palsy. Recently, we reported colocalization of phosphorylated α-synuclein (p-SNCA) and the largest subunit of dynactin (DCTN1) in Lewy body (LB)-like structures in Perry syndrome. Previous reports have not focused on the relationship between dynactin and synucleinopathies. Thus, we examined autopsied human brains from patients with Parkinson's disease, dementia with LBs, and multiple system atrophy using immunohistochemistry for p-SNCA, DCTN1, dynactin 2 (DCTN2, dynamitin) and dynein cytoplasmic 1 intermediate chain 1 (DYNC1I1). We also examined microtubule affinity-regulating kinases (MARKs), which phosphorylate microtubule-associated proteins and trigger microtubule disruption. Both brainstem-type and cortical LBs were immunopositive for DCTN1, DCTN2, DYNC1I1 and p-MARK and their staining often overlapped with p-SNCA. Lewy neurites were also immunopositive for DCTN1, DCTN2 and DYNC1I1. However, p-SNCA-positive inclusions of multiple system atrophy, which included both glial and neuronal cytoplasmic inclusions, were immunonegative for DCTN1, DCTN2, DYNC1I1 and p-MARK. Thus, immunohistochemistry for dynein-dynactin complex molecules, especially DCTN1, can clearly distinguish LBs from neuronal cytoplasmic inclusions. Our results suggest that dynactin is closely associated with LB pathology.

Original languageEnglish
Pages (from-to)583-590
Number of pages8
JournalNeuropathology
Volume38
Issue number6
DOIs
Publication statusPublished - Dec 2018

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Lewy Bodies
Cytoplasmic Dyneins
Pathology
Microtubules
Dyneins
Multiple System Atrophy
Phosphotransferases
Inclusion Bodies
Synucleins
Immunohistochemistry
Progressive Supranuclear Palsy
Motor Neuron Disease
Microtubule-Associated Proteins
Neurites
Dynactin Complex
Neuroglia
Neurodegenerative Diseases
Brain Stem
Parkinson Disease
Dementia

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Dynactin is involved in Lewy body pathology. / Shen, Chang; Honda, Hiroyuki; Suzuki, Satoshi O.; Maeda, Norihisa; Shijo, Masahiro; Hamasaki, Hideomi; Sasagasako, Naokazu; Fujii, Naoki; Iwaki, Toru.

In: Neuropathology, Vol. 38, No. 6, 12.2018, p. 583-590.

Research output: Contribution to journalArticle

Shen, C, Honda, H, Suzuki, SO, Maeda, N, Shijo, M, Hamasaki, H, Sasagasako, N, Fujii, N & Iwaki, T 2018, 'Dynactin is involved in Lewy body pathology', Neuropathology, vol. 38, no. 6, pp. 583-590. https://doi.org/10.1111/neup.12512
Shen, Chang ; Honda, Hiroyuki ; Suzuki, Satoshi O. ; Maeda, Norihisa ; Shijo, Masahiro ; Hamasaki, Hideomi ; Sasagasako, Naokazu ; Fujii, Naoki ; Iwaki, Toru. / Dynactin is involved in Lewy body pathology. In: Neuropathology. 2018 ; Vol. 38, No. 6. pp. 583-590.
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